VIRBAC PRODUCT GUIDE

Shaping the future of animal health TABLE OF CONTENTS

WHO IS VIRBAC Complete Product List with Product Numbers ...... 4-5 Introducing Stelfonta® ...... 6 Virbac is driven by a passion for enhancing the health of companion animals. Ear Health ...... 8 In the U.S., our focus is solely on meeting the unique needs of veterinary Skin Health ...... 9 professionals caring for dogs, cats and other companion animals. We Dental Health ...... 12 recognize that meeting those needs starts with listening. Heartworm ...... 17 Ultimately, the essence of Virbac U.S. is found in our relationships with our Parasiticides ...... 19 veterinarians. It is through these relationships that, together, we can find the Supplements ...... 22 right answers by first asking the right questions. Antibiotics ...... 24 In-Clinic Use ...... 25 Product Inserts/Disclosures ...... 27-39

If you have any questions regarding these products, please contact Virbac Veterinary us.virbac.com Technical Product Support at 1.800.338.3659 or your local Virbac Representative. PRODUCT LISTING PRODUCT LISTING

Product Description Product No. Size Product Description Product No. Size Product Description Product No. Size Product Description Product No. Size ANTIBIOTICS PAGE 24 DENTAL HEALTH PAGE 12 HEARTWORM PAGE 17 SUPPLEMENTS PAGE 22 BIOMOX® (amoxicillin) Oral Suspension (50 mg/mL) 92515 15 mL C.E.T. AQUADENT® FR3SH® Dental Solution 90508 8.45 fl oz. IVERHART MAX® Chew (ivermectin/pyrantel pamoate/praziquantel) - Display - Toy 50102 10 Boxes of 6 Doses ANXITANE® (L-Theanine) Chewable Tablets - S 50 mg 10432 30 ct. BIOMOX® (amoxicillin) Oral Suspension (50 mg/mL) 92530 30 mL C.E.T. AQUADENT® FR3SH® Dental Solution 90516 16.9 fl oz. IVERHART MAX® Chew (ivermectin/pyrantel pamoate/praziquantel) - Display - Small 50104 10 Boxes of 6 Doses ANXITANE® (L-Theanine) Chewable Tablets - M & L 100 mg 10435 30 ct. BIOMOX® (amoxicillin) Tablets (50 mg) 92505 500 ct. C.E.T.® Enzymatic Oral Hygiene Chews for Dogs - Extra Small 90601 Approx.30 ct. IVERHART MAX® Chew (ivermectin/pyrantel pamoate/praziquantel) - Display - Medium 50106 10 Boxes of 6 Doses MOVOFLEX® Soft Chews S (2 gm) 10700 60 ct. BIOMOX® (amoxicillin) Tablets (100 mg) 92105 500 ct. C.E.T.® Enzymatic Oral Hygiene Chews for Dogs - Small 90603 Approx.30 ct. IVERHART MAX® Chew (ivermectin/pyrantel pamoate/praziquantel) - Display - Large 50108 10 Boxes of 6 Doses MOVOFLEX® Soft Chews M (4 gm) 10701 60 ct. BIOMOX® (amoxicillin) Tablets (200 mg) 92205 500 ct. C.E.T.® Enzymatic Oral Hygiene Chews for Dogs - Medium 90605 Approx.30 ct. IVERHART PLUS® (ivermectin/pyrantel) Flavored Chewables - Display - Small 0170DS 10 Boxes of 6 Doses MOVOFLEX® Soft Chews L (6 gm) 10702 60 ct. CLINTABS® (clindamycin hydrochloride) Tablets (25 mg) 902540 400 ct. C.E.T.® Enzymatic Oral Hygiene Chews for Dogs - Large 90607 Approx.30 ct. IVERHART PLUS® (ivermectin/pyrantel) Flavored Chewables - Display - Medium 0170DM 10 Boxes of 6 Doses PANCREZYME® Powder 821008 8 oz. CLINTABS® (clindamycin hydrochloride) Tablets (75 mg) 907520 200 ct. C.E.T.® Enzymatic Tartar Control Toothpaste - Beef CET201 2.5 oz (70 g) IVERHART PLUS® (ivermectin/pyrantel) Flavored Chewables - Display - Large 0170DL 10 Boxes of 6 Doses PANCREZYME® Powder 821012 12 oz. CLINTABS® (clindamycin hydrochloride) Tablets (150 mg) 915010 100 ct. C.E.T.® Enzymatic Tartar Control Toothpaste - Seafood CET202 2.5 oz (70 g) SENERGY™ (selamectin) (30mg) 50005 10 Boxes of 3 Doses REBOUND® Recuperation Formula for Cats 10851 5.1 fl oz. RILEXINE® (cephalexin) Chewable Tablets (150 mg) 07620 100 ct. C.E.T.® Enzymatic Toothpaste - Malt CET102 2.5 oz (70 g) SENERGY™ (selamectin) (60mg) 50010 10 Boxes of 3 Doses REBOUND® Recuperation Formula for Dogs 10850 5.1 fl oz. RILEXINE® (cephalexin) Chewable Tablets (300 mg) 07630 100 ct. C.E.T.® Enzymatic Toothpaste - Poultry CET101 2.5 oz (70 g) SENERGY™ (selamectin) (120mg) 50020 10 Boxes of 3 Doses TUMIL-K® (potassium gluconate) Powder 846004 4 oz. RILEXINE® (cephalexin) Chewable Tablets (600 mg) 07640 100 ct. C.E.T.® Enzymatic Toothpaste - Vanilla-Mint CET103 2.5 oz (70 g) SENERGY™ (selamectin) (240mg) 50040 10 Boxes of 3 Doses TUMIL-K® (potassium gluconate) Tablets 845100 100 ct. C.E.T.® Enzymatic Toothpaste - Trial Packet Dispenser CET002 12 g/25 ct. SENERGY™ (selamectin) (360mg) 50085 10 Boxes of 3 Doses VETASYL® Fiber Capsules (500 mg) VF410 100 ct. EAR HEALTH PAGE 8 C.E.T.® HEXTRA® Premium Oral Hygiene Chews for Dogs - Petite 90612 Approx.30 ct. SENERGY™ (selamectin) (15mg) Dog & Cat 50090 10 Boxes of 3 Doses ® ® EASOTIC® (hydrocortisone aceponate, miconazole nitrate, 09360 10 mL C.E.T. HEXTRA Premium Oral Hygiene Chews for Dogs - Medium 90614 Approx.30 ct. SENERGY™ (selamectin) (45mg) Cat 50095 10 Boxes of 3 Doses IN-CLINIC USE PAGE 25 gentaminicin sulfate) Otic Suspension for Dogs ® ® C.E.T. HEXTRA Premium Oral Hygiene Chews for Dogs - Large 90616 Approx.30 ct. SENERGY™ (selamectin) (60mg) Cat 50097 10 Boxes of 3 Doses EUTHASOL® (pentobarbital sodium and phenytoin 710101 100 mL EPIOTIC™ Advanced Ear Cleanser 003104 4 fl oz. C.E.T.® HEXTRA® Premium Oral Hygiene Chews for Dogs - Extra Large 90618 Approx.30 ct. sodium) Euthanasia Solution ® EPIOTIC™ Advanced Ear Cleanser 003108 8 fl oz. C.E.T.® Oral Hygiene Kit w/70 gm Poultry CET401 1 each PARASITICIDES PAGE 19 STELFONTA (tigilanol tiglate injection) 2 mg/mL - Bottle 10101 1 mL ® ® OTOMITE PLUS Ear Miticide 601712 0.5 fl oz. ® SUPRELORIN F (deslorelin acetate) Implant (4.7 mg) x2 44402 2 ct. C.E.T. Oral Hygiene Kit for Cats w/70 gm Seafood CET402 1 each EFFIPRO PLUS® Topical Solution for Cats 60463 10 Boxes of 3 Doses ® ® SUPRELORIN F (deslorelin acetate) Implant (4.7 mg) x5 44405 5 ct. C.E.T. Dual-Ended Toothbrush CET305 1 each EFFIPRO PLUS® Topical Solution for Dogs - Small 60473 10 Boxes of 3 Doses ® SKIN HEALTH PAGE 9 C.E.T. Fingerbrush w/12 gm Trial Packet CET301 1 each EFFIPRO PLUS® Topical Solution for Dogs - Medium 60483 10 Boxes of 3 Doses ® ® ® ALLERDERM OMEGADERM Essential Fatty Acids Supplement 14149 4 mL (28 ct.) C.E.T. Mini-Toothbrush w/12 gm Trial Packet CET302 1 each EFFIPRO PLUS® Topical Solution for Dogs - Large 60503 10 Boxes of 3 Doses ® ® ® ALLERDERM OMEGADERM Essential Fatty Acids Supplement 14186 8 mL (28 ct.) C.E.T. Cat Toothbrush w/ 12 gm Trial Packet CET303 1 each EFFIPRO PLUS® Topical Solution for Dogs - X-Large 60513 10 Boxes of 3 Doses ® ® ALLERGROOM Shampoo 12208 8 fl oz. C.E.T. Pet Toothbrush CET304 1 each EFFITIX® PLUS Topical Solution for Dogs - Toy 60520 10 Boxes of 3 Doses ® ® ALLERGROOM Shampoo 12216 16 fl oz. C.E.T. Pet Toothbrush Bulk Dispenser CET350 24 ct. EFFITIX® PLUS Topical Solution for Dogs - Small 60522 10 Boxes of 3 Doses ® ® ® ALLERMYL (Piroctone Olamine) Medicated Shampoo 002409 8 fl oz. C.E.T. VEGGIEDENT Flex Tartar Control Chews for Dogs - Extra Small 90085 30 ct. EFFITIX® PLUS Topical Solution for Dogs - Medium 60524 10 Boxes of 3 Doses ® ® ® ALLERMYL (Piroctone Olamine) Medicated Shampoo 002417 16 fl oz. C.E.T. VEGGIEDENT Flex Tartar Control Chews for Dogs - Small 90086 30 ct. EFFITIX® PLUS Topical Solution for Dogs - Large 60526 10 Boxes of 3 Doses ® ® ® EPI-SOOTHE Cream Rinse 001808 8 fl oz. C.E.T. VEGGIEDENT Flex Tartar Control Chews for Dogs - Medium 90087 30 ct. EFFITIX® PLUS Topical Solution for Dogs - X-Large 60528 10 Boxes of 3 Doses ® ® ® EPI-SOOTHE Cream Rinse 001816 16 fl oz. C.E.T. VEGGIEDENT Flex Tartar Control Chews for Dogs - Large 90088 30 ct. KNOCKOUT® Area Treatment 612014 14 oz. ® ® ® ® EPI-SOOTHE Shampoo 11708 8 fl oz. C.E.T. VEGGIEDENT FR3SH Tartar Control Chews for Dogs - Extra Small 90055 30 ct. KNOCKOUT® E.S. Area Treatment 612216 16 oz. ® ® ® ® EPI-SOOTHE Shampoo 11716 16 fl oz. C.E.T. VEGGIEDENT FR3SH Tartar Control Chews for Dogs - Small 90056 30 ct. KNOCKOUT® Room & Area Fogger 612106 6 oz. ® ® ® ® GENESIS (triamcinolone acetonide) Topical Spray 410508 8 fl oz. C.E.T. VEGGIEDENT FR3SH Tartar Control Chews for Dogs - Medium 90057 30 ct. PREVENTIC® Tick Collar for Dogs - 18" 609526 1 each ® ® ® ® GENESIS (triamcinolone acetonide) Topical Spray 410500 16 fl oz. C.E.T. VEGGIEDENT FR3SH Tartar Control Chews for Dogs - Large 90058 30 ct. PREVENTIC® Tick Collar for Dogs - 25" 609525 1 each ® ® ® KERATOLUX (Piroctone Olamine) Medicated Shampoo 002009 8 fl oz. C.E.T. VEGGIEDENT Zen Tartar Control Chews for Dogs - Extra Small 90075 30 ct. VIRBANTEL® (pyrantel pamoate/praziquantel) Flavored Chewables - Small Dogs & Puppies 54030 50 ct. ® ® ® KERATOLUX (Piroctone Olamine) Medicated Shampoo 002017 16 fl oz. C.E.T. VEGGIEDENT Zen Tartar Control Chews for Dogs - Small 90076 30 ct. VIRBANTEL® (pyrantel pamoate/praziquantel) Flavored Chewables - Medium & Large Dogs 51114 50 ct. KETOCHLOR® (Chlorhexidine Gluconate, Ketoconazole) 002908 8 fl oz. C.E.T.® VEGGIEDENT® Zen Tartar Control Chews for Dogs - Medium 90077 30 ct. Medicated Shampoo C.E.T.® VEGGIEDENT® Zen Tartar Control Chews for Dogs - Large 90078 30 ct. KETOCHLOR® (Chlorhexidine Gluconate, Ketoconazole) 002916 16 fl oz. C.E.T.® IntelliDent™ Cat Bites 90700 90 ct. Medicated Shampoo

4 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 5 Discover an innovative alternative to surgery for the treatment of MCTs in dogs

STELFONTA® (tigilanol tiglate injection) is indicated for use in dogs for the treatment of non-metastatic cutaneous mast cell tumors and non-metastatic subcutaneous mast cell tumors located at or distal to the elbow or the hock. STELFONTA removes 75% of MCTs with a single treatment1 SEEING IS BELIEVING

Study design: A multicenter, randomized, controlled, investigator- and owner-masked clinical study in 123 client-owned dogs with MCT measuring ≤10 cm3. Effectiveness was evaluated using response evaluation criteria in solid tumors (RECIST), where complete response was defined as complete removal of the tumor. The dogs in the STELFONTA group were treated once at the start of the study, in addition to receiving concurrent medications. Patients in the STELFONTA-treated or control groups that complete did not achieve a complete response at Day 28 were eligible to receive a second treatment or a first treatment if the patient was in the original control group. All patients in both the STELFONTA-treated and control groups received concurrent medications. Patients that achieved a complete response at Day 28 in either phase were followed for response 12 weeks after the final treatment.1 *Complete response was defined as complete resolution of the tumor.1 † No evidence of tumor recurrence at the site of STELFONTA treatment. with just one treatment1 Treat MCTs with a single intratumoral

An exciting new way to treat mast cell tumors injection, without surgery or anesthesia (MCTs) with an intratumoral injection STELFONTA® (tigilanol tiglate injection) is indicated for use in dogs for the treatment of non-metastatic cutaneous mast cell tumors and non-metastatic subcutaneous mast cell tumors located at or distal to the elbow or the hock. 4 HOURS 7 DAYS 6 WEEKS Hours: visible changes

Days: tumor destruction

Weeks: tumor site typically healed

Learn more while earning CE credits. View the e-learning modules by using the camera on your smartphone to capture the QR code or by visiting https://vet-us.virbac.com/stelfonta. To place an order, contact your Virbac representative or call 1-844-4-VIRBAC (1-844-484-7222). See reference on page 25. EAR HEALTH SKIN HEALTH

EASOTIC® (hydrocortisone aceponate, KERATOLUX® (Piroctone Olamine) KETOCHLOR® (Chlorhexidine Gluconate, miconazole nitrate, gentamicin sulfate) Medicated Shampoo Ketoconazole) Medicated Shampoo Otic Suspension for Dogs • With S-I-S SKIN INNOVATIVE SCIENCE® • An antiseptic shampoo for the management • Effective, Innovative and Easy Technolog,y KERATOLUX is a unique cleanser of conditions responsive to ketoconazole or that removes scales, crusts and excessive oil on the chlorhexidine in dogs and cats. It is a unique cleanser • Proven results for the treatment of canine otitis externa skin surface of dogs and cats for management of that combines ingredients that help improve hair coat • Unique anti-inflammatory: Hydrocortisone Aceponate keratoseborrheic conditions. With regular bathing, and skin balance. (HCA) is a new-generation diester steroid having a KERATOLUX Shampoo helps manage normal sebum • Specifically designed to meet the needs of dogs and positive benefit/risk ratio production, resulting in a pleasant smell and healthy cats with skin microbial imbalances, its antiseptic and • Contains proven effective antimicrobial and appearance to the skin coat: cleansing properties help manage bacterial and fungal antifungal agents – Improves hair and skin balance skin infections in dogs and cats. • Features an ergonomically designed applicator – Removes excess sebum and scales – Neutralizes unpleasant odors • Shown to provide sustained treatment of otitis externa with 5 once-daily doses EPIOTIC® ADVANCED – Neutralizes unpleasant odors – Supports healthy skin with S-I-S SKIN INNOVATIVE SCIENCE® Technology • For use in dogs only Ear Cleanser – Supports healthy skin with ® – Reduces micro-organism adhesion (Glycotechnology) • Active ingredients: S-I-S SKIN INNOVATIVE SCIENCE Technology – hydrocortisone aceponate (1.11 mg/mL) • Ideal for supporting good ear health in dogs prone to – Provides micro-organism anti-adhesive effects – Promotes natural skin microbial defenses – miconazole nitrate (17.4 mg/mL) otitis externa—such as those that: (Glycotechnology) (Defensin technology) with natural plant extracts – gentamicin sulfate (1.5 mg/mL) – Have allergies, including atopic dermatitis – Contains plant extracts that promote natural skin Available in: – Get wet often (swimmers) Available in: microbial defenses (Defensin technology) by 8 fl oz (237 mL) SKU 002908 – Have floppy or droopy ears that favor moisture supporting the innate immune response – 16 fl oz (473 mL) SKU 002916 10 mL (10 doses) SKU 09360 accumulation antimicrobial peptides (AMPs) • Cleans gently and powerfully with neutral-pH, low- Important Safety Information – Promotes a healthy microbial balance in animals EASOTIC® (hydrocortisone aceponate, miconazole nitrate, gentamicin alcohol, non-stinging/non-irritating formula with keratoseborrheic conditions (Piroctone Olamine) sulfate) Otic Suspension for Dogs: For otic (ear) use in dogs only. • Can be used 2-3 times per week or daily Humans with known or suspected hypersensitivity to hydrocortisone, aminoglycoside antibiotics, or azole antifungals should not handle • Limits the bonding of microorganisms to the ear Available in: ALLERGROOM® Shampoo this product. Contraindicated in dogs with known or suspected channel surface 8 fl oz (237 mL) SKU 002009 hypersensitivity to corticosteroids, imidazole antifungals, or amino- • Gentle, soap-free moisturizing shampoo designed for • Facilitates the removal of cellular debris and excessive wax glycoside antibiotics. Do not use in dogs with known tympanic 16 fl oz (473 mL) SKU 002017 frequent use on normal to dry skin to optimize the skin membrane (ear drum) perforation. The safe use of EASOTIC Otic • Provides a drying effect and hair coat of dogs, cats and horses of any age. Suspension in dogs used for breeding purposes has not been • Keeps ears smelling fresh evaluated. Do not administer orally. For full prescribing information, Available in: contact Virbac at 1-800-338-3659 or visit us.virbac.com. Available in: 8 fl oz (237 mL) SKU 12208 See package insert at the end of the product guide for full product 4 fl oz (118 mL) SKU 003104 information. 16 fl oz (473 mL) SKU 12216 8 fl oz (237 mL) SKU 003108

OTOMITE PLUS® Ear Miticide

• For treatment of ear mites in dogs, cats, puppies and kittens over 12 weeks of age • Contains pyrethrins with 2 synergist ingredients: — piperonyl butoxide — n-Octyl bicycloheptene dicarboximide • Soothing olive oil base helps ingredients disperse and penetrate in the stratum corneum • Active ingredients: – 0.15% Pyrethrins – 1.50% Piperonyl Butoxide Technical – 0.48% n-Octyl bicycloheptene dicarboximide Available in: 0.5 fl oz (14.7 mL) SKU 601712

8 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 9 SKIN HEALTH SKIN HEALTH

ALLERMYL® (Piroctone Olamine) GENESIS® Topical Spray EPI-SOOTHE® Cream Rinse ALLERDERM® OMEGADERM® Medicated Shampoo (0.015% triamcinolone acetonide) Essential Fatty Acids Supplement • Formulated for dry and sensitive skin in dogs, cats • With S-I-S SKIN INNOVATIVE SCIENCE® Technology, • Controls pruritus associated with allergic dermatitis and horses of any age. This unique formula helps • A nutritional supplement containing omega-3 and ALLERMYL is a soothing shampoo for the in dogs restore natural skin oils and moisture, makes the hair omega-6 essential fatty acids coat more manageable and helps prevent tangles management of allergic skin conditions. Specifically • Low concentration (0.015%) of triamcinolone • Formulated for dogs and cats designed to meet the needs of dogs and cats with while adding a high sheen to the hair coat. acetonide in a topical spray with potent topical anti- • Once-daily supplement sensitive and itchy skin. ALLERMYL Medicated inflammatory action Available in: Shampoo is a unique micro-emulsified formulation • Ideal for maintaining healthy skin and hair coat 8 fl oz (237 mL) SKU 001808 that combines ingredients that help: Available in: • Pre-measured EZ-dose packets 16 fl oz (473 mL) SKU 001816 • High product acceptance and good stability – Maintain skin barrier integrity 8 fl oz (237 mL) bottle with sprayer SKU 410508 16 fl oz (478 mL) bottle with sprayer SKU 410500 – Provide moisturizing and soothing effects Available in: 28-count dispensers (Skin Lipid Complex combination) Important Safety Information 4 mL for small dogs and cats < 20 lbs SKU 14149 – Support healthy skin with S-I-S SKIN INNOVATIVE GENESIS® Topical Spray (0.015% triamcinolone acetonide): For use 8 mL for medium and large dogs > 20 lbs SKU 14186 SCIENCE® Technology on dogs only. Wear gloves when applying the product. The use of EPI-SOOTHE® Shampoo  this product on dogs less than eight pounds, less than one year – Reduce microorganism adhesion (Glycotechnology) of age, breeding, pregnant, or lactating has not been evaluated. • With SPHERULITES® Microcapsules is a natural oat- – Promote natural skin microbial defenses Adverse events of polyuria and polyphagia have been reported in grain derivative, soap-free shampoo designed for (Defensin Technology) supporting the immune <6% of dogs receiving treatment. For full prescribing information, contact Virbac at 1-800-338-3659 or visit us.virbac.com. sensitive skin in dogs, cats and horses of any age. response (Antimicrobial Peptides - AMPs) with natural plant extracts See package insert at the end of the product guide for full product Available in: information. – Promote a healthy microbial balance in animals 8 fl oz (237 mL) SKU 11708 with allergic skin conditions (Piroctone Olamine) 16 fl oz (473 mL) SKU 11716 Available in: 8 fl oz (237 mL) SKU 002409 16 fl oz (473 mL) SKU 002417

10 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 11 DENTAL HEALTH DENTAL HEALTH

THE FR3SH® FAMILY C.E.T. AQUADENT® FR3SH®

2 Dental Solution E FR S E N S A H E C.E.T.® VEGGIEDENT® FR3SH® E L

N • Daily water additive to fight the source of bad breath C

1

Tartar Control Chews for Dogs PERFORMANCE • Supports healthy teeth and gums by controlling plaque

in dogs and cats 3 • Multifunctional dental chew to support digestive health BA CE LAN • Combination of 3 natural ingredients: ® • Made with FR3SH Technology that delivers fresh – Erythritol: a natural sweetener, has a freshening breath and more effect in mouth • Just one chew per day reduces tartar and plaque – Inulin: a natural prebiotic to help control bad breath • Highly palatable – Pomegranate Extract: a natural antioxidant • Unique Z-shape allows the chew to reach front to back • For use in dogs and cats • Supports at-home dental care between professional Available in: cleanings 8.45 fl oz (250 mL) SKU 90508 Available in 30 chews per bag: 16.9 fl oz (500 mL) SKU 90516 Extra Small: < 11 lbs SKU 90055 Small: 11-22 lbs SKU 90056 Medium: 22-60 lbs SKU 90057 Large: > 60 lbs SKU 90058

C.E.T.® VEGGIEDENT® FLEX C.E.T.® VEGGIEDENT® ZEN Tartar Control Chews for Dogs Tartar Control Chews for Dogs C.E.T.® INTELLIDENT™ Cat Bites • Multifunctional dental chew to support joint health • Multifunctional dental chew to support mental well-being • Made with FR3SH® Technology that delivers fresh • Made with FR3SH® Technology that delivers fresh • Freshens the breath by controlling plaque and tartar breath and more breath and more with mechanical action • Formulated with BIOVAFLEX® eggshell membrane • Formulated with L-theanine • Results shown with only 3 bites per day • Just one chew per day reduces tartar and plaque • Just one chew per day reduces tartar and plaque • Crunchy porous texture to provide an effective clean • Highly palatable • Highly palatable Available in 90 bites per bag SKU 90700 • Unique Z-shape allows the chew to reach front to back • Unique Z-shape allows the chew to reach front to back • Supports at-home dental care between professional • Supports at-home dental care between professional cleanings cleanings Available in 30 chews per bag: Available in 30 chews per bag: Extra Small: < 11 lbs SKU 90085 Extra Small: < 11 lbs SKU 90075 Small: 11-22 lbs SKU 90086 Small: 11-22 lbs SKU 90076 Medium: 22-60 lbs SKU 90087 Medium: 22-60 lbs SKU 90077 Large: > 60 lbs SKU 90088 Large: > 60 lbs SKU 90078

12 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 13 DENTAL HEALTH DENTAL HEALTH

CHEWS & BITES C.E.T.® ORAL HYGIENE KIT for Cats C.E.T.® ORAL HYGIENE KIT for Dogs Seafood-flavor Toothpaste 2.5 oz (70 g) Poultry-flavor Toothpaste 2.5 oz (70 g) C.E.T.® ENZYMATIC C.E.T.® HEXTRA® • Contains: • Contains: ® Oral Hygiene Chews for Dogs Premium Oral Hygiene Chews for Dogs – C.E.T. Tartar Control Toothpaste – C.E.T.® Enzymatic Toothpaste ® – C.E.T. Finger Toothbrush – C.E.T.® Finger Toothbrush • Features an exclusive Dual-Enzyme System plus an • Natural rawhide coated with exclusive solution of – C.E.T.® Cat Toothbrush ® abrasive texture that works with the dog’s chewing Chlorhexidine that helps reduce plaque and tartar – C.E.T. Dual-Ended Toothbrush action to remove tartar and provide plaque control • Contains single layer beef hide for a natural abrasive Oral Hygiene Kit for Cats Seafood-flavor Oral Hygiene Kit for Dogs Poultry-flavor • Contains single layer beef hide for a natural abrasive cleansing action Toothpaste 2.5 oz (70 g) SKU CET402 Toothpaste 2.5 oz (70 g) SKU CET401 cleansing action • Appealing poultry flavor • Appealing poultry flavor • Chew size and thickness may vary Available in: Available in: Extra Small: < 11 lbs SKU 90601 Petite: < 11 lbs SKU 90612 Small: 11-22 lbs SKU 90603 Medium: 11-25 lbs SKU 90614 Medium: 22-60 lbs SKU 90605 Large: 26-50 lbs SKU 90616 Large: > 60 lbs SKU 90607 X-Large: > 50 lbs SKU 90618 Approximately 30 chews per bag (based on weight) Approximately 30 chews per bag (based on weight) C.E.T.® CAT TOOTHBRUSH with 12 g Trial Packet

• Contains: – C.E.T.® Cat Toothbrush – 0.4 oz (12 g) trial-size packet toothpaste in poultry Cat Toothbrush with .4oz (12 g) C.E.T.® CAT MINI-TOOTHBRUSH Trial Packet SKU CET303 with 12 g Trial Packet

• Contains: – C.E.T.® Mini-Toothbrush – 0.4 oz (12 g) trial-size packet toothpaste in poultry Cat Mini-Toothbrush with .4oz (12 g) Trial Packet SKU CET302 TOOTHPASTES, TOOTHBRUSHES AND KITS

C.E.T.® ENZYMATIC TOOTHPASTE C.E.T.® CAT FINGERBRUSH with 12 g Trial Packet • Formulated using an enzyme system to reduce plaque, freshen breath and ensure a clean mouth • Contains: • No foaming agents, so it is safe for pets to swallow – C.E.T.® Finger Toothbrush • Available in 5 flavors: Seafood, Malt, Beef, Poultry and – 0.4 oz (12 g) trial-size packet Vanilla-Mint toothpaste in poultry • Can be used for dogs and cats Cat Fingerbrush with .4oz (12 g) Available in: Trial Packet SKU CET301 2.5 oz (70 g) tube - Poultry SKU CET101 2.5 oz (70 g) tube - Malt SKU CET102 2.5 oz (70 g) tube - Vanilla-Mint SKU CET103 2.5 oz (70 g) tube - Beef SKU CET201 2.5 oz (70 g) tube - Seafood SKU CET 202 Poultry flavor is also available in 0.4 oz (12 g) trial-size packets in a 25-count dispenser SKU CET002

14 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 15 DENTAL HEALTH HEARTWORM

TOOTHPASTES, TOOTHBRUSHES AND KITS (continued) IVERHART MAX® Chew (ivermectin/ IVERHART PLUS® (ivermectin/ pyrantel pamoate/praziquantel) pyrantel) Flavored Chewables C.E.T.® FINGER TOOTHBRUSH C.E.T.® DUAL-ENDED TOOTHBRUSH • Prevents heartworm disease • Prevents heartworm disease • Ideal beginner toothbrush to help acquaint dogs, cats • Long handle with reverse angle allows for easy • Treats and controls roundworms, hookworms and • Treats and controls roundworm and and their owners with the tooth brushing experience application tapeworms hookworm infections in dogs • Convenient design and excellent pet acceptance • Tapered end conforms to pet’s mouth and teeth • Satisfaction guaranteed • Satisfaction guaranteed • Made of durable, • Dual-ended for large and small tooth surfaces • Administer once a month year-round • Administer once a month year-round dishwasher-safe material • Soft bristles assure a gentle, well-tolerated application • Bacon-flavored • Pork liver flavored • Helps remove plaque from tooth • Individually packaged, assorted colors Available in four sizes, depending on the dog’s weight: Available in three sizes, depending on the dog’s weight surface Toy: 6-12 lbs SKU 50102 Small: Up to 25 lbs SKU 0170DS • Massages and strengthens gums Small: 12.1-25 lbs SKU 50104 Medium: 26-50 lbs SKU 0170DM • Also contains a 0.4 oz (12 g) Medium: 25.1-50 lbs SKU 50106 Large: 51-100 lbs SKU 0170DL trial-size packet of poultry- Large: 50.1-100 lbs SKU 50108 flavored toothpaste 6-dose card display box / 10 cards per display (60 doses) 6-dose card display box / 10 cards per display (60 doses) C.E.T. Dual-Ended Toothbrush SKU CET305 Important Safety Information C.E.T. Oral Hygiene Kit for Dogs w/70g Poultry SKU CET401 Important Safety Information IVERHART PLUS® (ivermectin/pyrantel) Flavored Chewables is well C.E.T. Fingerbrush w/12g Trial pocket SKU CET301 IVERHART MAX® Chew (ivermectin/pyrantel pamoate/praziquantel) is tolerated. All dogs should be tested for heartworm disease before C.E.T. Oral Hygiene Kit for Cats w/70g Poultry SKU CET401 C.E.T. Oral Hygiene Kit for Cats w/70g Seafood SKU CET402 well tolerated. All dogs should be tested for heartworm disease starting a preventive protocol. There are rare reports of digestive or neurological side effects following use ofIVERHART PLUS Flavored C.E.T. Oral Hygiene Kit for Cats w/70g Seafood SKU CET402 before starting a preventive protocol. Following the use of IVERHART MAX® Chew, gastrointestinal and neurological side effects have been Chewables. For full prescribing information, contact Virbac at reported. For full prescribing information, contact Virbac at 1-800- 1-800-338-3659 or visit us.virbac.com. 338-3659 or visit us.virbac.com. See package insert at the end of the product guide for full product information. C.E.T.® MINI-TOOTHBRUSH C.E.T.® CAT TOOTHBRUSH

• Soft bristles for pet comfort and acceptance • Soft, gentle, easy to use • Small end and fingertip design • Long, soft bristles with a pointed tuft allow for easy access • Unique shape is designed for the limited confines • Also contains a 0.4 oz (12 g) of the feline mouth trial-size packet of poultry-flavored • Also contains a 0.4 oz (12 g) trial-size packet of toothpaste poultry-flavored toothpaste

C.E.T. Mini-Tooth brush w/12g Trial Packet SKU CET302

C.E.T. Cat Toothbrush w/12g Trial Packet SKU CET303 C.E.T. Oral Hygiene Kit for Cats w/70g Seafood SKU CET402

C.E.T.® PET TOOTHBRUSH

• Soft bristles for pet comfort and acceptance • Small end with reverse angle allows for easy application • Individually packaged, assorted colors • Available individually or in a 24 ct. dispenser

C.E.T. Pet Toothbrush SKU CET304 C.E.T. Pet Toothbrush Bulk Dispenser SKU CET350

16 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 17 HEARTWORM PARASITICIDES

SENERGY™ (selamectin) EFFIPRO® PLUS EFFITIX® PLUS for Cats and Dogs Topical Solution for Dogs Topical Solution for Dogs

Indications: • Dual action of fipronil and pyriproxyfen to break flea • Effective monthly application against fleas, flea eggs, • Kills adult fleas life cycle flea pupae, flea larvae, ticks and mosquitoes • Prevention and control of flea infestations • Kills fleas and ticks for up to one month for dogs and • Easy to apply, quick-drying, waterproof puppies • Prevention of heartworm disease • Repels and kills: • Only use on dogs and puppies 8 weeks or older • • Treatment and control of ear mites Adult fleas • DO NOT USE ON CATS • • Treatment and control of hookworms and All stages of Deer Tick, Brown Dog Tick, Lone Star Tick and American Dog Tick roundworms (cats only) Active ingredients: • Mosquitoes • Treatment and control of sarcoptic mange and • Fipronil control of tick infestations (dogs only) • Repels biting flies • Pyriproxyfen • Topical application • Starts working on contact • Kills fleas, flea eggs and flea larvae • Only once every 30 days EFFIPRO® PLUS Topical Solution for Dogs: • Quick drying DO NOT USE ON CATS. Read entire label before each use. Active ingredients: Available in 3 applications per carton: • Fipronil Kitten (at least 6 weeks old) and Puppy (at least 8 weeks old): Available in 3 applicators per carton: • Permethrin Up to 5 lbs SKU 50090 Small: 5-22.9 lbs SKU 60473 • Pyriproxyfen Cats: 5.1-15 lbs SKU 50095 Medium: 23-44.9 lbs SKU 60483 Cats: 15.1-22 lbs SKU 50097 Large: 45-88.9 lbs SKU 60503 EFFITIX® PLUS Topical Solution for Dogs: DO NOT USE ON CATS. Dogs, Toy: 5.1-10 lbs SKU 50005 X-Large: 89-132 lbs SKU 60513 Read entire label before each use. Dogs, Small: 10.1-20 lbs SKU 50010 Dogs, Medium: 20.1-40 lbs SKU 50020 Available in 3 applicators per carton: Dogs, Large: 40.1-85 lbs SKU 50040 Toy: 5-10.9 lbs SKU 60520 Dogs, X-Large: 85.1-130 lbs SKU 50085 Small: 11-22.9 lbs SKU 60522 10 boxes of 3 doses Medium: 23-44.9 lbs SKU 60524

Important Safety Information Large: 45-88.9 lbs SKU 60526 SENERGY™ (selamectin) may be irritating to the skin and eyes X-Large: 89-132 lbs SKU 60528 for people. Wash hands after use. Do not use in sick, debilitated or underweight animals. All dogs should be tested for heartworm disease before starting a preventive protocol. Use only on cats that are at least 8 weeks old and dogs that are at least 6 weeks old. For full prescribing information, contact Virbac at 1-800-338-3659 or visit us.virbac.com.

See package insert at the end of the product guide for full product information.

18 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 19 PARASITICIDES PARASITICIDES

EFFIPRO® PLUS KNOCKOUT® E.S. Area Treatment PREVENTIC® Tick Collar for Dogs Topical Solution for Cats • Inverted aerosol spray • Dual action of fipronil and pyriproxyfen to break flea • Contains pyrethrins and permethrin for control of adult • Tick collar for dogs life cycle fleas and ticks • Kills and detaches ticks for 3 months ® • Kills fleas and ticks for up to one month in catsand • Pyriproxyfen (Nylar insect growth regulator) for flea • Provides full protection against ticks within 48 hours kittens egg sterilization lasting up to 7 months of placement • Only use on cats and kittens 8 weeks or older • Contains the highest levels of environmental adulticides Active ingredients: • DO NOT USE ON DOGS, PUPPIES OR RABBITS in an aerosol for maximum effectiveness and quick • 9.0% amitraz • 1 convenient dose for cats and kittens weighing 1.5 killing of fleas and ticks pounds or more • Covers approximately 2100 square feet Do not use on puppies under 12 weeks of age. • Apply this product only as specified on the labeling. DO Active ingredients: PREVENTIC® TICK COLLAR FOR DOGS: NOT TREAT PETS WITH THIS PRODUCT. DO NOT USE ON CATS. • Fipronil Read entire label before each use. • Pyriproxyfen Available in: 16 oz (454 g) inverted aerosol can SKU 612216 Available in single collar in two sizes: EFFIPRO® PLUS Topical Solution for Cats: Read entire label before each use. 18” for dogs up to 60 lbs SKU 609526 KNOCKOUT® Room and Area Fogger 25” for dogs over 60 lbs SKU 609525 Available in 3 applicators per carton: For cats weighing 1.5 lbs and over SKU 60463 • Total release in-home fogger • Contains pyrethrins and permethrin to provide both quick and residual killing of adult fleas and ticks • Pyriproxyfen (Nylar®) insect growth regulator sterilizes fleas and their eggs for up to 7 months • Treats 6000 cubic feet • Apply this product only as specified on the labeling. VIRBANTEL® (pyrantel pamoate/ DO NOT TREAT PETS WITH THIS PRODUCT. praziquantel) Flavored Chewables Available in: 6 oz (170 g) size SKU 612106 • Flavored chewables to treat and control roundworms, hookworms and tapeworms in dogs and puppies 12 weeks and older KNOCKOUT® Area Treatment • Safety in breeding and pregnant dogs has not been evaluated • Contains pyrethrins and tetramethrin for quick kill of Available in 50-count bottles: adult fleas and ticks 30 mg for dogs 6.0-25 lbs SKU 54030 • Pyriproxyfen (Nylar®) insect growth regulator for flea 114 mg for dogs 25.1-200 lbs SKU 51114 egg sterilization lasting up to 4 months • Covers approximately 2000 square feet Important Safety Information • Apply this product only as specified on the labeling. VIRBANTEL® (pyrantel pamoate/praziquantel) Flavored Chewables: Do not use in sick animals. Safety in breeding dogs and pregnant DO NOT TREAT PETS WITH THIS PRODUCT. dogs has not been evaluated. For complete product insert, contact Virbac at 1-800-338-3659 or us.virbac.com. Available in: 14 oz (397 g) aerosol can See package insert at the end of the product guide for full product information. SKU 612014

20 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 21 SUPPLEMENTS SUPPLEMENTS

MOVOFLEX® Soft Chews ANXITANE® (L-THEANINE)  REBOUND® Recuperation Formula for Chewable Tablets Dogs and Cats • Joint supplement that is made up of a unique blend of ingredients that helps keep dogs in motion • Supplement for dogs and cats demonstrating signs of • Helps support pet’s nutrition needs during recuperation • Contain a proprietary blend of 5 ingredients, mild to moderate anxiety • Balanced, fortified nutrition in a low-calorie liquid formula including the following: • Promotes relaxation in cats and dogs exhibiting • Palatable and easy to administer ® nervousness, responding to environmentally induced – BIOVAFLEX Egg Shell membrane: supports • No added preservatives or colorants joint function stress or are anxious without causing drowsiness or • Can be used up to 14 days or until the dog/cat starts ® sedation – ZANTHIN natural astaxanthin: protects against to eat and drink normally free radicals • Containing a pure synthetic form of L-Theanine, • For use in dogs and cats – Boswellia serrata: supports the structure of joints an amino acid naturally found in green tea leaves, and connective tissue ANXITANE Tablets are a palatable option that both Available in: cats and dogs will enjoy – Hyaluronic acid: supports the viscosity of the Formula for Cats: 5.1 fl oz (150 mL) SKU 10851 synovial fluid Formula for Dogs: 5.1 fl oz (150 mL) SKU 10850 Not intended for use in animals with severe phobias, separation – Vitamin D3: supports healthy bones anxiety or in animals with a known history of aggression. • Easy to administer Available in 30-count box: Available in 50-count bottles: Small (dogs and cats 0-22 lbs); 50 mg tablets SKU 10432 Small: Up to 40 lbs (120 grams/4.2 oz) SKU 10700 Medium / Large (dogs >22 lbs and up); 100 mg tablets SKU 10435 Medium: > 40-80 lbs (240 grams/8.5 oz) SKU 10701 Large: Over 80 lbs (360 grams/12.7 oz) SKU 10702 TUMIL-K® (potassium gluconate) VETASYL® Fiber Capsules Tablets and TUMIL-K® (potassium • Natural fiber source – psyllium seed husks (95%) gluconate) Powder • Provides gentle support, proper digestion and bowel health in dogs and cats • For use as a supplement to support the health of the kidneys in cats and dogs with potassium deficiency • Barley malt extract powder for flavor Available in: Available in: Tablets in 100-count bottles SKU 845100 500 mg capsules in a 100-count bottle SKU VF410 Powder – 4 oz SKU 846004

PANCREZYME® Powder

• For use as a digestive aid in enzyme replacement where digestion of carbohydrates, protein and fat is inadequate • Provides standardized amylase, protease and lipase activities – plus esterases, peptidases, nucleases and elastase • Pancreatic enzyme concentrate derived from whole raw pancreas of porcine origin Available in: Powder – 8 oz. SKU 821008 Powder – 12 oz. SKU 821012

22 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 23 ANTIBIOTICS IN-CLINIC USE

BIOMOX® (amoxicillin tablets) & EUTHASOL® (pentobarbital sodium and STELFONTA® BIOMOX® (amoxicillin) Suspension phenytoin sodium) Euthanasia Solution (tigilanol tiglate injection) 1 mg/mL

• Broad-spectrum, veterinary-use antibiotic • Intravenous solution for humane, painless and rapid Treat MCTs with a single intratumoral injection, without • Bactericidal activity against a wide range of common euthanasia surgery or anesthesia. ® pathogens • For dogs only Stelfonta injection is indicated for use in dogs for the treatment of: non-metastatic cutaneous mast cell tumors and • Indicated for the treatment of soft tissue infections Available in: non-metastatic subcutaneous mast cell tumors located at or (abscesses, wounds, lacerations) for use in dogs only 100 mL multiple dose vials SKU 710101 distal to the elbow or the hock • Also indicated for bacterial dermatitis • Destroys 75% of the Mast Cell Tumors with just Important Safety Information Available in: EUTHASOL® (pentobarbital sodium and phenytoin sodium) one treatment 500-count bottles - 50 mg SKU 92505, 100 mg SKU 92105 Euthanasia Solution: WARNING: Keep out of reach of children. If • Complete wound healing at tumor site typically and 200 mg SKU 92205 eye contact, flush with water and seek medical advice/attention. CAUTION: Caution should be exercised to avoid contact of the drug healed in 28 days, with minimal intervention 15 mL SKU 92530 and 30 mL SKU 92515 suspension with with open wounds or accidental self-inflicted injections. For canine Available in: 50 mg/mL potency when reconstituted euthanasia only. Must not be used for therapeutic purposes. Do not RILEXINE® (cephalexin tablets) use in animals intended for food. Euthanasia may be delayed in dogs 2 mL vial SKU 10101 with severe cardiac or circulatory deficiencies. Important Safety Information Chewable Tablets BIOMOX® (amoxicillin) Oral Suspension: For use in dogs only. Important Safety Information ENVIRONMENTAL HAZARD: This product is toxic to wildlife. Contraindicated in animals with a history of an allergic reaction to Accidental self-injection of STELFONTA® (tigilanol tiglate injection) The first and only veterinary-approved cephalexin indicated Birds and mammals feeding on treated animals may be killed. penicillin. If an allergic reaction occurs seek veterinary treatment. Do may cause severe wound formation. To decrease the risk of accidental for the treatment of secondary superficial bacterial pyoderma Euthanized animals must be properly disposed of by deep burial, not use in pregnant or breeding animals. For complete information self-injection, sedation of the dog may be necessary. In dogs, do not incineration, or other method in compliance with state and local or to obtain a package insert, contact Virbac at 1-800-338-3659, or in dogs. inject STELFONTA into subcutaneous mast cell tumors located above laws, to prevent consumption of carcass material by scavenging visit us.virbac.com. the elbow or hock. Formation of wounds, possibly extensive, is an • Proven palatability means at-home dosing is easy for wildlife. For full prescribing information, contact Virbac at 1-800- intended and likely response to treatment with STELFONTA along with your clients 338-3659 or visit us.virbac.com. associated swelling, bruising, and pain; these wounds are expected Important Safety Information to heal. Appropriate pre- and post-treatment medications must be BIOMOX® (amoxicillin tablets): For use in dogs only. Contraindicated in • Available in three sizes of tablets and scored to make See full prescribing information for complete boxed warning. given, including a corticosteroid plus blocking agents for both H1 and animals with a history of an allergic reaction to penicillin. If an allergic it easy to prescribe the exact dose needed H2 receptors, in order to decrease the potential for severe systemic reaction occurs seek veterinary treatment. Do not use in pregnant or adverse reactions, including death, from mast cell degranulation. breeding animals. For complete information or to obtain a package Available in scored, flavored chewable tablets: insert, contact Virbac at 1-800-338-3659, or visit us.virbac.com. 150 mg (100 count) SKU 07620, 300 mg (100 count) SKU 07630 For full prescribing information, contact VIRBAC at 1-800-338-3659 See package inserts at the end of the product guide for full product and 600 mg (100 count) SKU 07640 or visit https://vet-us.virbac.com/stelfonta. information. CLINTABS® Tablets Important Safety Information (clindamycin hydrochloride tablets) RILEXINE® (cephalexin tablets) Chewable Tablets: For oral use in dogs only. People with sensitivities to penicillins or cephalosporins • Easy-to-swallow tablet form should avoid contact with this product. RILEXINE Chewable Tablets are very palatable for pets and should be stored in a secure location • A bacteriostatic antibiotic where pets cannot access them. Do not give to dogs with known indicated for the treatment allergy to penicillins or cephalosporins. Safety in pregnant females or of susceptible dental and breeding males has not been established. The most common adverse reactions in dogs include diarrhea, vomiting, anorexia and lethargy. skin infections (wounds and For full prescribing information, contact Virbac at 1-800-338-3659 or abscesses), and osteomyelitis visit us.virbac.com. for dogs only See package insert at the end of the product guide for full product Available in: information. 25 mg (400 tablets) SKU 902540, 75 mg (200 tablets) SKU 907520 and 150 mg (100 tablets) SKU 915010

Important Safety Information CLINTABS® Tablets (clindamycin hydrochloride tablets): Keep out of reach of children. Not for human use. Contraindicated in animals with a history of hypersensitivity to clindamycin or lincomycin. Do not use in rabbits, hamsters, guinea pigs, horses, chinchillas or ruminating animals. Use with caution in patients with very severe kidney or liver disease and in animals receiving neuromuscular blocking agents such STELFONTA: References 1. DeRidder TR, Campbell JE, Burke-Schwarz C, et al. Randomized controlled clinical study evaluating the efficacy and safety of intratumoral treatment as succinylcholine. Safety in pregnant females or breeding males has of canine mast cell tumors with tigilanol tiglate (EBC‐46). J Vet Intern Med. Published June 16, 2020. doi: 10.1111/jvim.15806. 2. Welle MM, Bley CR, Howard J, Rüfenacht S. Canine not been established. Monitor blood work in animals on either high mast cell tumours: a review of the pathogenesis, clinical features, pathology and treatment. Vet Dermatol. 2008;19:321–339. 3. Garrett LD. Canine mast cell tumors: diagnosis, dose or prolonged therapy. Side effects occasionally observed include treatment, and prognosis. Vet Med (Auckl). 2014;5:49–58. 4. Dobson JM, Scase TJ. Advances in the diagnosis and management of cutaneous mast cell tumours in dogs. J Small Anim Prac. 2007;48:424–431. 5. Śmiech A, Łopuszyński W, Ślaska B, Bulak K, Jasik A. Occurrence and distribution of canine cutaneous mast cell tumour characteristics among vomiting and diarrhea. For full prescribing information, contact Virbac predisposed breeds. J Vet Res. 2019;63:141–148. 6. Lowe R, Gavazza A, Impellizeri JA, Soden DM, Lubas G. The treatment of canine mast cell tumours with electrochemotherapy at 1-800-338-3659 or visit us.virbac.com. with or without surgical excision. Vet Comp Oncol. 2017;15:775–784. 7. Kiupel M, Camus M. Diagnosis and prognosis of canine cutaneous mast cell tumors. Vet Clin North Am Small Anim Pract. 2019;49:819–836. 8. Monteiro B, Boston S, Monteith G. Factors influencing complete tumor excision of mast cell tumors and soft tissue sarcomas: a retrospective See package insert at the end of the product guide for full product study in 100 dogs. Can Vet J. 2011;52:1209–1214. 9. Brodbelt D. Perioperative mortality in small animal anaesthesia. Vet J. 2009;182:152–161. 10. STELFONTA US packaging insert. 2020. information. 11. Melo S, Januário E, Pinto AC. Intra-tumoral injection of tigilanol tiglate in canine mast cell tumors: time-assessed thermographic images, computed tomography and clinical response. In: Proceedings of the Veterinary Cancer Society Conference 2019; October 17–19, 2019; Houston, TX.

24 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 25 IN-CLINIC USE PRODUCT INSERTS/DISCLOSURES

Approved by FDA under NADA # 065-495 CONTRAINDICATIONS: Use of amoxicillin is contraindicated in animals with a SUPRELORIN® F (deslorelin acetate) history of an allergic reaction to penicillin. ® IMPLANT BIOMOX (amoxicillin) ADVERSE REACTIONS: Amoxicillin is a semisynthetic penicillin and, therefore, has the potential for producing allergic reactions. Epinephrine and/or steroids Veterinary For Oral Suspension • For the management of adrenal gland cortical disease should be administered if an allergic reaction occurs. For use in DOGS only. WARNINGS: For use in dogs only. (ACD) in the male and female domestic ferret DESCRIPTION: BIOMOX® (amoxicillin) is a broad-spectrum, semisynthetic antibiotic which provides bactericidal activity against a wide range of common PRECAUTIONS: Until adequate reproductive studies are accomplished, Biomox • Reduces clinical signs of ACD with a return to gram-positive and gram-negative pathogens. Amoxicillin chemically is D-(-) (amoxicillin) for oral suspension should not be used in pregnant or breeding normalcy in 2-8 weeks1-2 α-amino-p-hydroxybenzyl penicillin trihydrate. animals. Inactive Ingredients: Cherry Flavor, Silicon Dioxide NF, FD&C Red #40, CAUTION: Federal law restricts this drug to use by or on the order of a licensed • 4.7-mg dose implant has been shown to be well- Polyoxyethylene-Polyoxypropylene Glycol, Sodium Benozate, Sodium Citrate, veterinarian. 1 tolerated with clinical monitoring Sodium Saccharin, and Sucrose. DOSAGE AND ADMINISTRATION: The recommended dosage is 5 mg per • Simple: A single subcutaneous implant is ACTION: Amoxicillin has bactericidal activity against susceptible organisms pound of body weight administered twice daily for 5 to 7 days. Continue for 48 similar to that of ampicillin. It acts by inhibiting the biosynthesis of bacterial hours after all symptoms have subsided. If no improvment is noted in 5 days, the recommended once per year wall mucopeptides. Most strains of the following gram-positive and gram- diagnosis should be reconsidered and therapy changed. • Convenient: Dissolves without intervention, so no negative bacteria have demonstrated susceptibility to: amoxicillin, both in DIRECTIONS FOR MIXING ORAL SUSPENSION: Add sufficient water to vitro and in vivo: nonpenicillinase-producing staphylococci, alpha- and beta- the bottle as indicated in the table below and shake vigorously. Each mL of removal is necessary hemolytic streptococci, Streptococcus faecalis, Escherichia coli and Proteus suspension will contain 50 mg of amoxicillin as the trihydrate. mirabilis. Amoxicillin does not resist destruction by penicillinase; therefore, it is not effective against penicillinase-producing bacteria, particularly resistant Amount of Water Available in: staphylococci. Most strains of Enterobacter and klebsiella and all strains of Bottle Size to Add for Reconstitution 2-count SKU 44402 Pseudomonas are resistant. 15 mL 11 mL 5-count SKU 44405 Amoxicillin may be given without regard to meals because it is stable in gastric 30 mL 21 mL acid. It is rapidly absorbed following oral administration and diffuses readily into Note: When stored at room temperature or in refrigerator, discard unused portion most body fluids and tissues. It diffuses poorly into the brain and spinal fluid Important Safety Information of reconstituted suspension after 14 days. except when the meninges are inflamed. Most of the amoxicillin is excreted in ® SUPRELORIN® F (deslorelin acetate) Implant: For use in ferrets only. DO 1. Wagner RA, Piché CA, Jöchle W, Oliver JW. Clinical and endocrine responses to SUPPLY: Bimox (amoxicillin) for oral suspension is supplied in bottles treatment with deslorelin acetate implants in ferrets with adrenocortical disease. the urine unchanged. containing 0.75 g of amoxicillin activity in bottles of 15 mL or 1.5 g of amoxicillin NOT HANDLE THIS PRODUCT IF YOU ARE PREGNANT OR NURSING Am J Vet Res. 2005;66(5):910–914. INDICATIONS: BIOMOX® (amoxicillin) for oral suspension is indicated in the activity in bottles of 30 mL. After reconstitution with the required amount of OR SUSPECT YOU MAY BE PREGNANT. Accidental administration in 2. Wagner RA, Finkler MR, Fecteau KA, Trigg TE. The treatment of adrenal treatment of the following infections in dogs when caused by susceptible strains water, each mL will contain 50 mg of amoxicillin as the trihydrate. humans may lead to disruption of the menstrual cycle. Do not use cortical disease in ferrets with 4.7 mg deslorelin acetate implants. J Exotic Pet Med. of organisms: 2009;18(2):146–152. Manufactured for: in animals intended for breeding. The safe use of this product has BACTERIAL DERMATITIS due to Staphylococcus aureus, Streptococcus spp.; Virbac AH, Inc. not been evaluated in pregnant or lactating ferrets. Do not use this Staphylococcus spp.; and E. coli. P.O. Box 162059 product in ferrets with known hypersensitivity to deslorelin acetate SOFT TISSUE INFECTIONS (abscesses, wounds, lacerations) due to Fort Worth, TX 76161 or other synthetic hormones. For full prescribing information, contact Staphylococcus aureus, Streptococcus spp.; E. coli, Proteus mirabilis and 1 - 800 - 338 - 3659 Virbac at 1-800-338-3659 or visit us.virbac.com. Staphylococcus spp. As is true with all antibiotic therapy, appropriate in vitro cultures and sensitivities 92515 07/19 Rev.-03 See package insert at the end of the product guide for full product should be conducted prior to treatment. information. Approved by FDA under NADA # 065-492 Enterococcus faecalis, Escherichia coli, Proteus mirabilis, and ® Staphylococcus spp. BIOMOX With all antibiotic therapy, appropriate in vitro cultures and sensitivities (amoxicillin tablets) should be conducted prior to treatment. For use in DOGS only. CONTRAINDICATIONS: Use of amoxicillin is contraindicated in DESCRIPTION: animals with a history of an allergic reaction to penicillin. BIOMOX® (amoxicillin tablets) are a broad-spectrum, semisynthetic ADVERSE REACTIONS: antibiotic which provides bactericidal activity against a wide range of Amoxicillin is a semisynthetic penicillin and, therefore, has the common gram-positive and gram-negative pathogens. Amoxicillin potential for producing allergic reactions. Epinephrine and/or steroids chemically is D-(-)α-amino-p-hydroxybenzyl penicillin trihydrate. should be administered if an allergic reaction occurs. Inactive Ingredients: WARNINGS: Dibasic Calcium Phosphate Dihydrate, Magnesium Stearate, For use in dogs only. Microcrystalline Cellulose and Sodium Starch Glycolate. PRECAUTIONS: ACTION: Until adequate reproductive studies are accomplished, Amoxicillin has bactericidal activity against susceptible organisms Biomox® (amoxicillin tablets) should not be used in pregnant or similar to that of ampicillin. It acts by inhibiting the biosynthesis of breeding animals. bacterial cell wall mucopeptides. Most strains of the following gram- positive and gram-negative bacteria have demonstrated susceptibility CAUTION: to amoxicillin, both in vitro and in vivo: nonpenicillinase-producing Federal law restricts this drug to use by or on the order of a staphylococci, alpha- and beta- hemolytic streptococci, Enterococcus licensed veterinarian. faecalis, Escherichia coli and Proteus mirabilis. Amoxicillin does not DOSAGE AND ADMINISTRATION: resist destruction by penicillinase; therefore, it is not effective against The recommended dosage is 5 mg per pound of body weight penicillinase-producing bacteria, particularly resistant staphylococci. administered twice daily for 5 to 7 days or 48 hours after all symptoms Most strains of Enterobacter and Klebsiella and all strains of have subsided. If no improvement is noted in 5 days, the diagnosis Pseudomonas are resistant. Amoxicillin may be given without regard should be reconsidered and therapy changed. to meals because it is stable in gastric acid. It is rapidly absorbed SUPPLY: following oral administration and diffuses readily into most body fluids Biomox® (amoxicillin tablets) are supplied in 50 mg, 100 mg and 200 and tissues. It diffuses poorly into the brain and spinal fluid except mg concentrations in bottles of 500 tablets. when the meninges are inflamed. Most of the amoxicillin is excreted in Manufactured for: the urine unchanged. Virbac AH, Inc. INDICATIONS: P.O. Box 162059 ® BIOMOX (amoxicillin tablets) are indicated for treatment of the Fort Worth, TX 76161 following infections in dogs when caused by susceptible strains of 1 - 800 - 338 - 3659 organisms: Printed in USA Rev. -06 05/19 BACTERIAL DERMATITIS due to Staphylococcus aureus, Strepto-coccus ©2019 Virbac Corporation. All Rights Reserved. spp., Staphylococcus spp., and Escherichia coli. BIOMOX is a registered trademark of Virbac AH, Inc. SOFT TISSUE INFECTIONS (abscesses, wounds, lacerations) due to Staphylococcus aureus,

26 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 27 PRODUCT INSERTS/DISCLOSURES PRODUCT INSERTS/DISCLOSURES

(hydrocortisone aceponate, miconazole nitrate, gentamicin sulfate) PHARMACOLOGY Otic Suspension for Dogs Hydrocortisone aceponate is a glucocorticoid with anti-inflammatory Anti-inflammatory, antifungal, and antibacterial effects. Miconazole nitrate is an imidazole antifungal. Gentamicin sulfate is an aminoglycoside antibiotic. Rx For Otic Use in Dogs Only In the target animal safety study, hydrocortisone aceponate, miconazole Award-winning bottle design* shown to improve owner compliance and gentamicin were shown to be systemically absorbed from the ears of 3 CAUTION healthy dogs (see ANIMAL SAFETY); increased systemic absorption may be (P=0.0081) with canine otitis externa treatments. Federal law restricts this drug to use by or on the order of a licensed observed in inflamed ears. veterinarian. MICROBIOLOGY DESCRIPTION ® The compatibility and additive effect of each of the components in EASOTIC Otic Suspension contains 1.11 mg/mL hydrocortisone aceponate, EASOTIC® Otic Suspension was demonstrated in a component effectiveness 17.4 mg/mL miconazole nitrate and 1.5 mg/mL gentamicin (as sulfate). The and non-interference study. An in vitro study of organisms collected from inactive ingredient is a semi-liquid petroleum jelly. clinical cases of otitis externa in dogs and from dogs enrolled in the clinical effectiveness study for EASOTIC Otic Suspension determined that INDICATIONS miconazole nitrate and gentamicin sulfate inhibit the growth of bacteria EASOTIC Otic Suspension is indicated for the treatment of otitis externa in and yeast commonly associated with otitis externa in dogs. No consistent dogs associated with susceptible strains of yeast (Malassezia pachydermatis) synergistic or antagonistic effect of the two antimicrobials was and bacteria (Staphylococcus pseudintermedius). demonstrated. The addition of hydrocortisone aceponate to the combination did not impair antimicrobial activity to any DOSAGE AND ADMINISTRATION clinically-significant extent. Verify that the tympanic membrane is intact. Shake well before each use. In a field study (see EFFECTIVENESS), the minimum of 10 isolates from Priming the canister: Prior to the first use of the dosing canister, prime the successfully treated cases was met for S. pseudintermedius and M. pump by depressing the pump 1 to 2 times to fill the clear canula (tip) with a pachydermatis. full dose of product. Carefully insert the canula into the affected external ear canal(s) and apply 1 EFFECTIVENESS mL (a single pump) of Otic Suspension once per day for 5 days. Wash hands The effectiveness of this drug was evaluated in 157 dogs with otitis externa. after usage. The study was a double-masked field study with a placebo control. One hundred and four dogs were treated with EASOTIC Otic Suspension and CONTRAINDICATIONS 53 dogs were treated with the placebo control. Treatment was administered Do not use in dogs with known tympanic membrane perforation. once daily for 5 consecutive days to the affected ear(s). The dogs were EASOTIC Otic Suspension is contraindicated in dogs with known or suspected evaluated at 4 different intervals over the course of 1 month to determine hypersensitivity to corticosteroids, imidazole antifungals, or aminoglycoside response to therapy. The 6 clinical signs evaluated were: malodor, aural antibiotics. discharge, pruritus, erythema, swelling and pain. The individual clinical scores were assigned based on the severity of each sign. Success was based WARNINGS on clinical improvement at Day 28 ±2 days. The success rates of the 2 Human Warnings: Not for use in humans. Keep this and all drugs out of reach groups were significantly different (p=0.0179); 68.5% of dogs administered of children. In case of accidental skin contact, wash area thoroughly with EASOTIC Otic Suspension were successfully treated, compared to 21.8% of water. Avoid contact with eyes. the dogs in the placebo control group. Humans with known or suspected hypersensitivity to hydrocortisone, ANIMAL SAFETY aminoglycoside antibiotics, or azole antifungals should not handle this In the target animal safety study, EASOTIC Otic Suspension was product. administered at 0X, 1X, 3X and 5X the recommended dose for 15 In case of accidental ingestion by humans, contact a physician immediately. consecutive days (3 times the recommended treatment duration) in Physicians may contact a Poison Control Center for advice concerning cases of laboratory Beagles, with 8 dogs per group. Hypersensitivity reactions in the ingestion by humans. external ear canal and inner pinnae were seen in all EASOTIC Otic Animal Warnings: As a class, aminoglycoside antibiotics are associated with Suspension groups and included mild to severe aural erythema (3X group), papules and ulceration (1X and 5X groups), otitis externa (3X and 5X ototoxicty, vestibular dysfunction and renal toxicity. The use of EASOTIC groups), and otitis media (5X group). Renal tubular crystals were present in Otic Suspension in a dog with a damaged tympanic membrane can result the cortex and medulla (0X, 1X, 3X, and 5X groups) and mild renal tubular in damage to the structures of the ear associated with hearing and balance basophilia and atrophy were present in one 5X group dog. Baseline cortisol or in transmission of the infection to the middle or inner ear. Immediately values and the cortisol response to ACTH stimulation were lower in treated discontinue use of EASOTIC Otic Suspension if hearing loss or signs of dogs compared to the control dogs. The ACTH stimulation test results are vestibular dysfunction are observed during treatment (see ADVERSE consistent with systemic absorption of topical corticosteroids causing REACTIONS). suppression of the hypothalamic-pituitary-adrenal axis. Dogs in the 3X and 5X groups demonstrated elevations in AST and ALP, while dogs in the 1X, PRECAUTIONS 3X, and 5X groups had elevated cholesterol, total protein, and albumin Do not administer orally. levels. Dogs in the 3X and 5X groups also had higher liver weights and greater food consumption. Concurrent administration of potentially ototoxic drugs should be avoided. Use with caution in dogs with impaired hepatic or renal function (see STORAGE INFORMATION: Store at temperatures between 20o C-25o C o o o o o o ANIMAL SAFETY). (68 F-77 F), with excursions permitted between 15 C-30 C (59 F-86 F). Long-term use of topical otic corticosteroids has been associated with adrenocortical suppression and iatrogenic hyperadrenocorticism in dogs HOW SUPPLIED: EASOTIC Otic Suspension is supplied in a polyethylene (see ANIMAL SAFETY). canister, with a soft applicator canula. The safe use of EASOTIC Otic Suspension in dogs used for breeding purposes, during pregnancy, or in lactating bitches, has not been Each canister contains ten 1 mL doses.Made in the U.S.A. evaluated.

ADVERSE REACTIONS Distributed by: In a field study conducted in the United States (see EFFECTIVENESS), there Virbac AH, Inc. were no adverse reactions reported in 145 dogs administered EASOTIC Otic P.O. Box 162059 Supsension. Fort Worth, TX 76161 USA In foreign market experience, reports of hearing loss and application site erythema have been received. In most reported cases, the hearing loss NADA 141-330, Approved by FDA. and erythema were transient and resolved with discontinuation of ® EASOTIC suspension. Revision Date 7/2017 To report suspected adverse drug events, contact Virbac at 800-338-3659 or the FDA at 1-888-FDA-VETS. © 2017 Virbac Corporation. All Rights Reserved. For technical assistance or to obtain a Safety Data Sheet, call Virbac at EASOTIC is a registred trademark of Virbac S.A. 800-338-3659. 302076-03

28 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 29 PRODUCT INSERTS/DISCLOSURES PRODUCT INSERTS/DISCLOSURES

If adverse clinical signs are observed, treatment should be discontinued. Once the signs have disappeared, treatment can be resumed at a lower dose or frequency of application. If hypersensitivity to the product occurs, treatment should be discontinued and appropriate therapy GENESIS instituted. In the presence of dermatological infections, use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, the TOPICAL SPRAY corticosteroid should be discontinued until the infection has been adequately controlled.

Solution of 0.015% triamcinolone acetonide. ADVERSE REACTIONS FOR TOPICAL USE IN DOGS ONLY. In a field study with GENESIS Topical Spray, polyuria was reported in 3 of 57 dogs (5.3%) and polyphagia in 1 of 57 dogs (1.8%). Mild (within reference range) decreases in total leukocyte, CAUTION lymphocyte and eosinophil counts were also reported. The following local reactions were reported CAUTION: Federal law (USA) restricts this drug to use by or on the order of a licensed veterinarian. in ≤ 3.6% of 110 dogs treated with GENESIS Topical Spray or the product vehicle: aversion/ discomfort, sneezing and watery eyes. DESCRIPTION GENESIS® Topical Spray contains 0.015% triamcinolone acetonide for dermatologic use. Each EFFECTIVENESS mL of GENESIS Topical Spray contains 0.15 mg triamcinolone acetonide in an aqueous solution In a 28-day field study to demonstrate the effectiveness of GENESIS Topical Spray in controlling containing propylene glycol, specially denatured alcohol, and DMDM hydantoin. pruritus associated with allergic dermatitis in dogs under field conditions, 105 dogs with atopy, unspecified allergic dermatitis, flea allergy, and food allergy were treated with GENESIS Topical PHARMACOLOGY Spray at the recommended use level or placebo. Results are shown in Table 2. Triamcinolone acetonide is highly potent synthetic glucocorticoid, which is primarily effective because of its anti-inflammatory activity. Topical corticosteroids can be absorbed from normal intact skin. Studies have demonstrated that topical preparations of triamcinolone have decreased Table 2. Percent of cases considered treatment successes plasma cortisol levels and suppressed the response to ACTH. Treatment Percent success1 INDICATIONS GENESIS Topical Spray 35/54 = 64.8%* GENESIS Topical Spray is indicated for the control of pruritus associated with allergic dermatitis in dogs. Placebo 12/51 = 23.5% 11 277 DOSAGE AND ADMINISTRATION Apply sufficient pump sprays to uniformly and thoroughly wet the affected areas while avoiding 1Success = reduction in the level of severity by two or run-off of excess product. Avoid getting the spray in dog’s eyes. GENESIS Topical Sprays should be more grades in the investigator’s overall evaluation from administered twice daily for seven days, once daily for the next seven days, then every other day the pre-treatment to the post-treatment evaluation period. for an additional 14 days (28 days total). *Significantly different from placebo at p < 0.05 To avoid overdosing the product, use the following table to determine the maximum number of pump sprays per treatment application. For mild pruritus or for small treatment surface areas, the number of pumps used should be less than this maximum amount. STORAGE CONDITIONS Table 1. Maximum allowable dosage Store at room temperature, 15° - 30° C (59° - 86° F).

Maximum HOW SUPPLIED Dog Weight Total maximum number of pumps GENESIS Topical Spray is supplied in 8 ounce (237 mL) and 16 ounce (478 mL) bottles with spray volume (mL) per per single applicators. 28 day treatment regimen lb kg application* For technical information or to report adverse reactions, please call (800) 338 - 3659. 11 5 4 101 22 10 7 176 33 15 11 277 Approved by FDA under NADA # 141-210. 44 20 15 378 55 25 19 478 (one 16-oz bottle) Manufactured by: 66 30 22 554 Virbac AH, Inc. 77 35 26 655 Fort Worth, TX 76137 USA 88 40 30 756 Phone: 1-800-338-3659 99 45 33 832 © 2019 Virbac Corporation. 110 50 37 932 (two 16-oz bottles) GENESIS is a registered trademark of Virbac Corporation. 750033 - 04 *Using the recommended dosing regimen, there are two applications per day for the first week, Rev. 01/2019 one application per day for the second week and one application every other day for the last two weeks of treatment.

WARNINGS User Safety: Wear gloves when applying the product. Spray in a well ventilated area. If the spray causes irritation to mucous membranes, discontinue use. Keep this and all drugs out of reach of children. Animal Safety: Clinical and experimental data have demonstrated that corticosteroids administered orally or by injection to animals may induce the first stage of parturition if used during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis. Additionally, corticosteroids administered to dogs, rabbits, and rodents during pregnancy have resulted in cleft palates in offspring. Corticosteroids administered to dogs during pregnancy have also resulted in other congenital anomalies including deformed forelegs, phocomelia, and anasarca.

PRECAUTIONS The safety of this product for dogs less than eight pounds or for dogs less than one year of age has not been evaluated. The safety of this product in breeding, pregnant or lactating dogs has not been evaluated (see WARNINGS). The safety of long term or repeated use of this product (greater than 28 days) has not been evaluated. Prolonged use or overdosage of any corticosteroid may produce adverse effects. Because absorption of triamcinolone acetonide through topical application on the skin and by licking may occur, dogs receiving triamcinolone acetonide therapy should be observed closely for evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression. When the product was applied at approximately 6 times the maximum allowable dose (100 mL) once daily to normal skin of two dogs for five days, plasma cortisol levels were decreased after the first treatment and response to ACTH was reduced.

30 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 31 PRODUCT INSERTS/DISCLOSURES PRODUCT INSERTS/DISCLOSURES

Adverse Reactions: In a field study with IVERHART MAX Chew, self-limiting adverse reactions, ACCEPTABILITY: In a trial in client-owned dogs, IVERHART PLUS Flavored Chewables including vomiting, diarrhea, lethargy, difficulty swallowing, excessive salivation, increased water were shown to be a palatable oral dosage form consumed at first offering by the majority consumption, and coughing were reported. Self-limiting adverse reactions, including lethargy, of dogs. limpness, salivation, shaking, diarrhea, decreased appetite, licking lips, and belching were reported between 20 minutes and 72 hours following treatment in a field study with ivermectin/pyrantel All dogs should be tested for existing heartworm infection before starting pamoate/praziquantel tablets. Flavored Chewables PRECAUTIONS: treatment with IVERHART PLUS Flavored Chewables, which are not effective against adult In field studies with ivermectin/pyrantel/praziquantel pamoate tablets, vomiting or diarrhea within D. immitis. Infected dogs must be treated to remove adult heartworms and microfilariae 24 hours of dosing was rarely observed (1.1% of administered doses). The following adverse For oral use in dogs only. Caution: Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian. before initiating a program with IVERHART PLUS Flavored Chewables. reactions have been reported in dogs following the use of ivermectin products: depression/lethargy, For use in dogs to prevent canine heartworm disease by eliminating the tissue stage Caution: Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian. vomiting, anorexia, diarrhea, mydriasis, ataxia, staggering, convulsions, and hypersalivation. INDICATIONS: While some microfilariae may be killed by the ivermectin in IVERHART PLUS Flavored of tissue stage of heartworm larvae (Dirofilaria immitis) for a month (30 days) after infection and ® To report suspected adverse events, for technical assistance or to obtain a copy of the Safety Data Chewables at the recommended dose level, IVERHART PLUS Flavored Chewables are not Description: IVERHART MAX Chew is a combination of three anthelmintics (ivermectin/pyrantel for the treatment and control of ascarids (Toxocara canis, Toxascaris leonina) and hookworms Sheet (SDS), contact Virbac AH, Inc. at 1-800-338-3659 or us.virbac.com. For additional information effective for microfilariae clearance. A mild hypersensitivity-type reaction, presumably due pamoate/praziquantel). The chews are available in four sizes in color-coded packages for oral (Ancylostoma caninum, Uncinaria stenocephala, Ancylostoma braziliense). administration to dogs according to their weight (see Dosage and Administration). about adverse drug experience reporting for animal drugs, contact the FDA at 1-888-FDA-VETS or to dead or dying microfilariae and particularly involving a transient diarrhea, has been www.fda.gov/reportanimalae. DOSAGE: IVERHART PLUS® (ivermectin/pyrantel) Flavored Chewables should be administered observed in clinical trials with ivermectin alone after treatment of some dogs that have Indications: For use in dogs to prevent canine heartworm disease by eliminating the tissue stage of orally at monthly intervals at the recommended minimum dose level of 6 mcg of ivermectin per circulating microfilariae. heartworm larvae (Dirofilaria immitis) for a month (30 days) after infection and for the treatment and Effectiveness: Prevention of the tissue larval stage of heartworm (Dirofilaria immitis) and the kilogram (2.72 mcg/lb) and 5 mg of pyrantel (as pamoate salt) per kg (2.27 mg/lb) of body weight. control of roundworms (Toxocara canis, Toxascaris leonina), hookworms (Ancylostoma elimination of the adult stage of hookworm (Ancylostoma caninum, Uncinaria stenocephala, caninum, Uncinaria stenocephala, Ancylostoma braziliense), and tapeworms (Dipylidium caninum, Anyclostoma braziliense), roundworm (Toxocara canis, Toxascaris leonina), and tapeworm The recommended dosing schedule for prevention of canine heartworm disease and for the Keep this and all drugs out of the reach of children. In case of ingestion by humans, Taenia pisiformis). (Dipylidium caninum, Taenia pisiformis) infections in dogs was demonstrated in well-controlled treatment and control of ascarids and hookworms is as follows: clients should be advised to contact a physician immediately. Physicians may contact a laboratory studies. Poison Control Center for advice concerning cases of ingestion by humans. Dosage and Administration: IVERHART MAX Chew should be administered orally at monthly intervals and the recommended minimum dose level of 6 mcg of ivermectin per kilogram (2.72 Palatability: In a field study of 132 dogs, IVERHART MAX Chew was offered once monthly for 3 Flavored Store at 20°C - 25°C (68°F - 77°F), excursions permitted between 15°C - 30°C (59°F - 86°F). months. The dogs voluntarily consumed 86.3% of the doses from the owner’s hand or from a bowl mcg/lb), 5 mg of pyrantel (as pamoate salt) per kg (2.27 mg/lb) and 5 mg of praziquantel per kg Dog Chewable Ivermectin Pyrantel Protect product from light. (2.27 mg/lb) of body weight, as follows: within 5 minutes, 13.0% accepted the dose when it was offered in food or administered by placing in the back of the dog’s tongue (pilling), and 0.7% of the doses were unable to be administered. Weight Per Month Content Content Pyrantel Warnings: Use product on or before its expiration date. Dog Weight Chew per Ivermectin Pamoate Praziquantel Animal Safety: Studies with ivermectin indicate that certain dogs of the Collie breed are more Up to 25 lbs 1 68 mcg 57 mcg Discard or return unused tablets. Pounds Month Chew Size Content Content Content sensitive to the effects of ivermectin administered at elevated dose levels (more than 16 times the target dose level of 6 mcg/kg) than dogs of other breeds. At elevated doses, sensitive dogs showed 26 to 50 lbs 1 136 mcg 114 mcg ADVERSE REACTIONS: In clinical trials with ivermectin/pyrantel, vomiting or diarrhea 6.0 to 12 1 Toy 34 mcg 28.5 mg 28.5 mg more adverse reactions which included mydriasis, depression, ataxia, tremors, drooling, paresis, within 24 hours of dosing was rarely observed (1.1% of administered doses). The following recumbency, excitability, stupor, coma and death. No signs of toxicity were seen at 10 times the 51 to 100 lbs 1 272 mcg 227 mcg adverse reactions have been reported following the use of ivermectin: Depression/lethargy, 12.1 to 25 1 Small 68 mcg 57 mg 57 mg recommended dose (27.2 mcg/lb) in sensitive Collies. Data from these studies support the safety of vomiting, anorexia, diarrhea, mydriasis, ataxia, staggering, convulsions and ivermectin products in dogs, including Collies, when used at the label recommended dose. 25.1 to 50 1 Medium 136 mcg 114 mg 114 mg hypersalivation. Because ivermectin and praziquantel are approximately 30% more bioavailable in the IVERHART PLUS are recommended for dogs 6 weeks of age and older. 50.1 to 100 1 Large 272 mcg 228 mg 228 mg MAX Chew than in the ivermectin/pyrantel pamoate/praziquantel tablets used in the following target IVERHART Flavored Chewables For dogs over 100 lbs use the appropriate combination of these flavored chewables. To report suspected adverse drug events, for technical assistance or to obtain a copy of animal safety studies, the margin of safety is narrower than reported in these studies. The potential the Safety Data Sheet (SDS), contact Virbac AH, Inc at 1-800-338-3659 or us.virbac.com. IVERHART MAX Chew is recommended for dogs 8 weeks of age or older. For dogs over 100 lbs, use for adverse reactions may be greater in individual dogs administered IVERHART MAX Chew than For additional information about adverse drug experience reporting for ADMINISTRATION: Remove only one flavored chewable at a time from the foil-backed the appropriate combination of these soft chews. ivermectin/pyrantel pamoate/praziquantel tablets. animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae. blister card. Because most dogs find IVERHART PLUS Flavored Chewables palatable, the Remove only one dose at a time from the packaging. Return the remaining chew(s) to their box to In a target animal safety study using ivermectin/pyrantel pamoate/praziquantel tablets, doses were product can be offered to the dog by hand. Alternatively, it may be added intact to a small protect from light. The chew can be offered to the dog by hand or added, intact, to a small amount administered to 8 week old Beagle puppies at one, three, and five times the maximum recommended amount of dog food or placed in the back of the dog's mouth for forced swallowing. SAFETY: Studies with ivermectin indicate that certain dogs of the Collie breed are more of dog food. Care should be taken to ensure that the dog consumes the complete dose. The treated dose of 12.5 mcg/kg ivermectin, 10.47 mg/kg pyrantel and 10.47 mg/kg praziquantel. The dogs sensitive to the effects of ivermectin administered at elevated dose levels (more than 16 dog should be observed for a few minutes after administration to confirm that none of the dose has were treated every 30 days for 6 months. Vomiting within 6 hours of dosing and soft or watery feces times the target use level of 6 mcg/kg) than dogs of other breeds. At elevated doses, Care should be taken that the dog consumes the complete dose, and treated animals been lost or rejected. If it is suspected that any of the dose has been lost, redosing within 24 hours of dosing were observed. Other observations during the study were: ano-genital sensitive dogs showed adverse reactions which included mydriasis, depression, ataxia, swelling, lethargy, head movements, shallow, audible or difficult breathing, and salivation. One dog in should be observed for a few minutes after administration to ensure that part of the dose is recommended. is not lost or rejected. If it is suspected that any of the dose has been lost, redosing is tremors, drooling, paresis, recumbency, excitability, stupor, coma and death. lvermectin the 5X group had tremors and decreased activity. All of these signs were transient. No treatment was demonstrated no signs of toxicity at 10 times the recommended dose (60 mcg/kg) in IVERHART MAX Chew should be given at monthly intervals during the period of the year when recommended. required. Histopathology showed testicular hypoplasia in the 3X and 5X groups (see Warnings). sensitive Collies. Results of these trials and bioequivalency studies, support the safety of mosquitoes (vectors), potentially carrying infective heartworm larvae, are active. The initial dose must ivermectin products in dogs, including Collies, when used as recommended. be given within a month (30 days) after the dog’s first exposure to mosquitoes. The final dose must be In a laboratory safety study using ivermectin/pyrantel pamoate/praziquantel tablets, 12-week- IVERHART PLUS Flavored Chewables should be given at monthly intervals during the given within a month (30 days) after the dog’s last exposure to mosquitoes. old Beagle puppies receiving 3 and 5 times the recommended dose once weekly for 13 weeks period of the year when mosquitoes (vectors), potentially carrying infective heartworm demonstrated a dose-related decrease in testicular maturation compared to controls. In this study, larvae, are active. The initial dose must be given within a month (30 days) after the dog’s lvermectin/pyrantel has shown a wide margin of safety at the recommended dose level in When replacing another heartworm preventative product in a heartworm disease prevention all treated puppies had significantly higher cholesterol levels compared to untreated controls. dogs, including pregnant or breeding bitches, stud dogs and puppies aged 6 or more program, the first dose of IVERHART MAX Chew must be given within a month (30 days) after the first exposure to mosquitoes. The final dose must be given within a month (30 days) after In a reproductive safety study, adult males were treated at 37.5 mcg/kg ivermectin, 31.4 mg/kg the dog’s last exposure to mosquitoes. weeks. In clinical trials, many commonly used flea collars, dips, shampoos, anthelmintics, last dose of the former medication. A heartworm test should be performed prior to and 6 months antibiotics, vaccines and steroid preparations have been administered with after switching heartworm preventative products. pyrantel and 31.4 mg/kg praziquantel every 14 days during two full spermatogenic cycles (112 days). The quality of semen and reproductive health were not affected by treatment. Treatment When replacing another heartworm preventive product in a heartworm disease ivermectin/pyrantel in a heartworm disease preventive program. If the interval between doses exceeds a month (30 days), the effectiveness of ivermectin can be related vomiting and soft feces were reported during this study. preventive program, the first dose of IVERHART PLUS Flavored Chewables must be given reduced. Therefore, for optimal performance, the chew must be given once a month on or about within a month (30 days) of the last dose of the former medication. In one trial, where some pups had parvovirus, there was a marginal reduction in efficacy the same day of the month. If treatment is delayed, whether by a few days or many, immediate In a study of the effectiveness of ivermectin/pyrantel pamoate/praziquantel tablets for the treatment against intestinal nematodes, possibly due to a change in intestinal transit time. treatment with IVERHART MAX Chew and resumption of the recommended dosing regimen will of Toxocara canis, one 8.1 lb, 72-day-old puppy died 6 days after administration of the label dose. This puppy and many other puppies in the study had high worm burdens and were reported to have If the interval between doses exceeds a month (30 days), the efficacy of ivermectin can be minimize the opportunity for the development of adult heartworms. PLUS are available in three dosage diarrhea, sometimes bloody, frequently before and after treatment. Dehydration and signs of anemia reduced. Therefore, for optimal performance, the flavored chewable must be given once a HOW SUPPLIED: IVERHART Flavored Chewables Warnings: (pale mucous membranes) were the only abnormal gross necropsy finding observed. No definitive month on or about the same day of the month. If treatment is delayed, whether by a few strengths (See DOSAGE section) for dogs of different weights. Each strength comes in a box of 6 tablets, packed 10 boxes per display box. For use in dogs only. Keep this and all drugs out of reach of children and pets. In safety cause was determined. In a 90-day field study using ivermectin/pyrantel pamoate/praziquantel days or many, immediate treatment with IVERHART PLUS Flavored Chewables and studies with ivermectin/pyrantel pamoate/praziquantel tablets, testicular hypoplasia was tablets, the most serious adverse reactions (lethargy, limpness, and salivation) were seen in dogs resumption of the recommended dosing regimen minimizes the opportunity for the observed in some dogs receiving 3 and 5 times the maximum recommended dose monthly weighing less than 10 lbs (see Precautions). development of adult heartworms. Approved by FDA under ANADA # 200-302 for 6 months (see Animal Safety). Storage Information: Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C In case of ingestion by humans, clients should be advised to contact a physician immediately. and 30°C (59°F to 86°F). Protect product from light. Monthly treatment with IVERHART PLUS Flavored Chewables also provides effective Manufactured by: Physicians may contact a Poison Control Center for advice concerning cases of ingestion by humans. treatment and control of ascarids (T. canis, T. leonina) and hookworms (A. caninum, U. How Supplied: IVERHART MAX Chew is available in four dosage strengths (see Dosage and stenocephala, A. braziliense). Clients should be advised of measures to be taken to prevent Virbac AH, Inc. Precautions: Use with caution in sick, debilitated, or underweight animals and dogs weighing less Administration) for dogs of different weights. Each strength comes in a package of 6 chews. Fort Worth, TX 76137, USA than 10 lbs (see Animal Safety). The safe use of this drug has not been evaluated in pregnant or reinfection with intestinal parasites. lactating bitches. Approved by FDA under NADA # 141-441 EFFICACY: IVERHART PLUS Flavored Chewables, given orally using the recommended dose All dogs should be tested for existing heartworm infection before and 6 months after starting and regimen, are effective against the tissue larval stage of D. immitis for a month (30 days). treatment with IVERHART MAX Chew, which is not effective against adult Dirofiliaria immitis. Manufactured by: after infection and, as a result, prevent the development of the adult stage. Infected dogs should be treated to remove adult heartworms and microfilariae before initiating a © 2020 Virbac Corporation. 301732-04 heartworm prevention program. IVERHART PLUS is a registered trademark of Virbac Corporation. 12/2020 Virbac AH, Inc. IVERHART PLUS Flavored Chewables are also effective against canine ascarids (T. canis, T. Fort Worth, TX 76137 USA While some microfilariae may be killed by the ivermectin in IVERHART MAX® Chew at the leonina) and hookworms (A. caninum, U. stenocephala, A. braziliense). Phone: 1-800-338-3659 recommended dose level, IVERHART MAX Chew is not effective for microfilariae clearance. A mild hypersensitivity-type reaction, presumably due to dead or dying microfilariae and particularly involving a transient diarrhea, has been observed in clinical trials with ivermectin alone after © 2020 Virbac Corporation. treatment of some dogs that have circulating microfilariae. IVERHART MAX is a registered trademark of Virbac Corporation. 302143-04 10/2020

Shaping the future of animal health

32 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 33 PRODUCT INSERTS/DISCLOSURES PRODUCT INSERTS/DISCLOSURES

® A summary of the pharmacokinetics (PK) observed in fed and fasted Beagle dogs administered a single 22 mg/kg SENERGY™ (selamectin) Package mg per Potency Administered Ear Mite Treatment in Dogs and Cats RILEXINE dose is provided in Table 2. Cats (lb) Topical Parasiticide For Dogs and Cats Color tube (mg/mL) volume (mL) For the treatment of ear mite (O. cynotis) infestations in dogs (cephalexin tablets) Table 2: Pharmacokinetics Parameter values (mean ± standard deviation), protein-corrected in fasted and fed dogs Up to 5 Mauve 15 mg 60 0.25 and cats, SENERGY should be administered once as a single following a single administration of 22 mg/kg dose of RILEXINE Chewable Tablets (N = 12) Chewable Tablets CAUTION: 5.1–15 Blue 45 mg 60 0.75 topical dose. A second monthly dose may be required in some dogs. Monthly use of SENERGY will control any subsequent ear Antimicrobial for Oral Use in Dogs only US Federal law restricts this drug to use by or on the order of 15.1–22 Taupe 60 mg 60 1.0 Parameter FASTED FED mite infestations. In the clinical field trials ears were not cleaned, CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Mean ± SD1 Mean ± SD1 a licensed veterinarian. and many animals still had debris in their ears after the second ® For cats over 22 lbs use the appropriate combination of tubes. DESCRIPTION: RILEXINE Chewable Tablets are a chewable, bisected tablet supplied in 3 sizes containing 150mg, AUCINF_obs DESCRIPTION: dose. Cleansing of the infested ears is recommended to remove 300 mg, and 600 mg of cephalexin. Cephalexin is a cephalosporin, beta-lactam, broad spectrum antibiotic. Thefull (mg.h/L) 105.36 ± 17.31 108.35 ± 25.85 chemical name for cephalexin is 7-(D-a-amino- a-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid SENERGY (selamectin) Topical Parasiticide is available as a Package mg per Potency Administered the debris. monohydrate. AUClast colorless to yellow, ready to use solution in single dose tubes Dogs (lb) (mg.h/L) 97.33 ± 13.18 95.19 ± 11.84 Color tube (mg/mL) volume (mL) Sarcoptic Mange Treatment in Dogs for topical (dermal) treatment of dogs six weeks of age and older Up to 5 Mauve 15 mg 60 0.25 Cmax (mg/L) 21.66 ± 2.74 16.99 ± 2.71 and cats eight weeks of age and older. The content of each tube For the treatment of sarcoptic mange (S. scabiei) in dogs, 5.1–10 Lavender 30mg 120 0.25 SENERGY should be administered once as a single topical dose. T1/2(h) 7.33 ± 4.30 8.79 ± 6.44 is formulated to provide a minimum of 2.7 mg/lb (6 mg/kg) of body 10.1–20 Brown 60 mg 120 0.5 Tmax (h) 1.42 ± 0.42 1.17 ± 0.25 weight of selamectin. The chemical composition of selamectin A second monthly dose may be required in some dogs. Monthly 1SD = Standard Deviation is (5Z,25S)-25-cyclohexyl-4’-O-de(2,6-dideoxy-3-O-methyl-α-L- 20.1–40 Red 120 mg 120 1.0 use of SENERGY will control any subsequent sarcoptic mange INDICATION: For the treatment of secondary superficial bacterial pyoderma in dogs caused by susceptible strains of 40.1–85 Teal 240 mg 120 2.0 mite infestations. Because of the difficulty in finding sarcoptic Staphylococcus pseudintermedius. Cephalosporins are associated with time dependent killing effects. Accordingly, the pharmacodynamic arabino-hexopyranosyl)-5-demethoxy-25-de(1-methylpropyl)-22, (PD) target is time above MIC (T>MIC). For staphylococcal infections, the goal for time above MIC is 23-dihydro-5-hydroxyiminoavermectin A . 85.1–130 Plum 360 mg 120 3.0 mange mites on skin scrapings, effectiveness assessments also DOSAGE AND ADMINISTRATION: The recommended dose is 22 mg/kg (10 mg/lb) 1a were based on resolution of clinical signs. Resolution of the 40% of the dosing interval (which translates to 4.8 hrs for a BID dosing schedule). For streptococcal of body weight twice daily for 28 days. infections, the target for time above MIC is 60% of the dosing interval (i.e., 7.2 hrs). To assess whether INDICATIONS: For dogs over 130 lbs use the appropriate combination of tubes. pruritus associated with the mite infestations was observed in Appropriate culture and susceptibility tests should be performed before treatment to determine the causative or not the PK-PD target is met with a 22 mg/kg BID dosing regimen under fed and fasted conditions, it SENERGY is recommended for use in dogs six weeks of age or Recommended for use in dogs 6 weeks of age and older and in approximately 50% of the dogs 30 days after the first treatment organism and its susceptibility to cephalexin. Therapy withRILEXINE Chewable Tablets may be initiated before results was assumed that the MIC90 for S. pseudintermedius is 2 µg/mL. Plasma drug concentrations were normalized to cats 8 weeks of age and older. and in approximately 90% of the dogs 30 days after the second of these tests are known; once the results become available, antimicrobial therapy should be adjusted accordingly. exactly 22 mg/kg dose and corrected for 10% protein binding (protein binding observed in canine plasma). older and cats eight weeks of age and older for the following parasites and indications: monthly treatment. If acceptable response to treatment is not observed, then the diagnosis should be re-evaluated and Under fasted conditions, all targets were met in all dogs after the first daily dose. With food, the target for S. aureus asw ADMINISTRATION: appropriate alternative therapy considered. met by the second daily dose. Therefore, a 22 mg/kg BID dosing interval under fed or fasted conditions succeededin Dogs: A veterinarian or veterinary technician should demonstrate or Tick Control in Dogs attaining the PK-PD targets. CONTRAINDICATIONS: RILEXINE Chewable Tablets are contraindicated in dogs with a known allergy tocephalexin or SENERGY kills adult fleas and prevents flea eggs from hatching instruct the pet owner regarding the appropriate technique for For the control of tick (Dermacentor variabilis) infestations in to the -lactam (any of the penicillins or cephalosporins) group of antibiotics. β MICROBIOLOGY: Cephalexin is a cephalosporin antibiotic. Like other β-lactam antimicrobials, cephalexin exerts for one month and is indicated for the prevention and control of applying SENERGY topically to dogs and cats prior to first use. dogs, SENERGY should be administered on a monthly basis. In its inhibitory effect by interfering with bacterial cell wall synthesis. This interference is primarily due to its covalent WARNINGS: For use in dogs only. Not for use in humans. Keep this drug out of the reach of children.Antimicrobials, flea infestations (Ctenocephalides felis), prevention of heartworm Remove the tube from the package and hold upright with the lot heavy tick infestations, complete efficacy may not be achieved including penicillins and cephalosporins, can cause allergic reactions in sensitized individuals. Sensitized individuals binding to the penicillin-binding proteins (PBPs) (i.e., transpeptidase and carboxypeptidase), which are essential handling such antimicrobials, including cephalexin, should avoid contact of the product with the skin and mucous for synthesis of the bacterial wall. Minimum Inhibitory Concentrations (MICs) for cephalexin against label-claim disease caused by Dirofilaria immitis, and the treatment and and expiration at the bottom. Bend the tip back until it snaps off. after the first dose. In these cases, one additional dose may be membranes in order to minimize the risk of allergic reactions. pathogens isolated from canine pyoderma in a 2008-2009 U.S. field trial are presented in Table 3. All MICs were control of ear mite (Otodectes cynotis) infestations. SENERGY To administer the product, part the hair on the back of the animal administered two weeks after the previous dose, with monthly determined in accordance with the Clinical Laboratory Standards Institute (CLSI) standards. at the base of the neck in front of the shoulder blades until the dosing continued thereafter. In case of ingestion by humans contact a physician immediately. Physicians may contact a poison control center for also is indicated for the treatment and control of sarcoptic mange Table 3: Summary of Cephalexin MIC values against S. pseudintermedius isolates from 88 dogs treated with (Sarcoptes scabiei) and for the control of tick infestations due to skin is visible. Place the tip of the tube on the skin and squeeze advice concerning cases of ingestion by humans. ® Nematode Treatment in Cats RILEXINE Chewable Tablets for bacterial pyoderma in a U.S. field study during 2008-2009 Dermacentor variabilis. the tube 3 or 4 times to empty its entire contents directly onto the To obtain a copy of the Safety Data Sheet (SDS), or to report adverse reactions, call Virbac at 1-800-338-3659. skin in one spot. Keeping the tube squeezed, drag it away from the For the treatment and control of intestinal hookworm PRECAUTIONS: Prescribing antibacterial drugs in the absence of a proven or strongly suspected bacterial infection is Microbial Cats: (A. tubaeforme) and roundworm (T. cati) infections, Time of MIC MIC MIC liquid and lift to remove. Check the tube to ensure that it is empty. unlikely to provide benefit to treated animals and may increase the risk of the development of drug-resistant animal Treatment 50 90 Range Sampling μg/mL μg/mL SENERGY kills adult fleas and prevents flea eggs from hatching Do not massage the product into the skin. Due to alcohol content, SENERGY should be applied once as a single topical dose. pathogens. Outcome μg/mL for one month and is indicated for the prevention and control of do not apply to broken skin. Avoid contact between the product SAFETY: RILEXINE Chewable Tablets are designed to taste good. Store RILEXINE Chewable Tablets out of reach ofdogs, cats, Success Pre- flea infestations (Ctenocephalides felis), prevention of heartworm * 1 2 1-2 and fingers. Do not apply when the haircoat is wet. Bathing or and other pets in a secured location. Post approval experience has shown that dogs and cats may willingly consume (n = 61) treatment disease caused by Dirofilaria immitis, and the treatment and Selamectin has been tested safe in over 100 different pure and more than the recommended dosage of RILEXINE Chewable Tablets, which can result in overdose. Adverse reactions shampooing the dog 2 or more hours after treatment will not mixed breeds of healthy dogs and over 15 different pure and mixed Pre- 1 2 1-8 control of ear mite (Otodectes cynotis) infestations. SENERGY may occur if large quantities of tablets are ingested (seeAdverse Reactions, Animal Safety, and Information for Dog treatment reduce the effectiveness of SENERGY against fleas or heartworm. breeds of healthy cats, including pregnant and lactating females, Owners sections). If the product is dispensed in a container other than the original, prescribers should consider adding Failure is also indicated for the treatment and control of roundworm Bathing or shampooing the cat 2 hours after treatment will not Post- breeding males and females, puppies six weeks of age and older, a statement on the bottle label reminding the owner that RILEXINE Chewable Tablets are designed to taste good and (n = 27)** (Toxocara cati) and intestinal hookworm (Ancylostoma reduce the effectiveness of SENERGY against fleas. Bathing or should be stored out of reach of pets in a secured location. treatment 2 16 1-32 tubaeforme) infections in cats. kittens eight weeks of age and older, and avermectin-sensitive (n = 17) shampooing the cat 24 hours after treatment will not reduce the collies. A kitten, estimated to be 5–6 weeks old (0.3 kg), died The safe use of RILEXINE Chewable Tablets in dogs intended for breeding and in pregnant or lactating bitches has effectiveness of SENERGY against heartworm. Stiff hair, clumping not been evaluated. *No post-treatment sampling was conducted due to the absence of lesions. WARNINGS: 8 1/2 hours after receiving a single treatment of selamectin at the **Of the 27 failures, 10 did not have positive post-treatment cultures. of hair, hair discoloration, or a slight powdery residue may be Not for human use. Keep out of the reach of children. recommended dosage. The kitten displayed clinical signs which Positive direct Coombs’ test results and false positive reactions for glucose in the urine have been reported during observed at the treatment site in some animals. These effects treatment with some cephalosporin antimicrobials. Cephalosporin antimicrobials may also cause falsely elevated EFFECTIVENESS: The clinical effectiveness of RILEXINE Chewable Tablets was established in a randomized, multi- In humans, SENERGY may be irritating to skin and eyes. included muscle spasms, salivation and neurological signs. The location, placebo-controlled field study (see Table 4). In this study, 131 dogs with secondary superficial bacterial are temporary and do not affect the safety or effectiveness of the urine protein determinations. Some antimicrobials, including cephalosporins, can cause lowered albumin values due Reactions such as hives, itching and skin redness have been kitten was a stray with an unknown history and was malnourished to interference with certain testing methods. pyoderma treated with either RILEXINE Chewable Tablets (n = 91) at 22 mg/kg (10 mg/lb) body weight or with a product. Discard empty tubes in your ordinary household refuse. negative control (n = 40), twice daily for 28 days, were analyzed.RILEXINE Chewable Tablets were considered superior reported in humans in rare instances. Individuals with known and underweight (see WARNINGS). 1 Occasionally, cephalosporins have been associated with myelotoxicity, thereby creating a toxic neutropenia. Other to the placebo (70% success rate vs. 13% respectively) in the treatment of secondary superficial bacterial pyoderma hypersensitivity to SENERGY should use the product with caution Flea Control in Dogs and Cats DOGS: In safety studies, selamectin was administered at 1, 3, 5, hematological reactions observed with cephalosporin therapy include neutropenia, anemia, caused by susceptible strains of S. pseudintermedius. or consult a health care professional. SENERGY contains isopropyl hypoprothrombinemia, thrombocytopenia, prolonged prothrombin time (PT) and partial thromboplastin time (PTT), For the prevention and control of flea infestations, SENERGY should and 10 times the recommended dose to six-week-old puppies, platelet dysfunction, and transient increases in serum aminotransferases2. Table 4: Primary endpoint: Percentage of Cure* in the Effectiveness population alcohol and the preservative butylated hydroxytoluene (BHT). be administered at monthly intervals throughout the flea season, and no adverse reactions were observed. The safety of selamectin ADVERSE REACTIONS: The most common adverse reactions in dogs include diarrhea, vomiting, anorexia and Wash hands after use and wash off any product in contact with starting one month before fleas become active. In controlled administered orally also was tested in case of accidental oral RILEXINE the skin immediately with soap and water. If contact with eyes ingestion. Oral administration of selamectin at the recommended lethargy. To report suspected adverse reactions call Virbac at 1-800-338-3659. Treatment Tablets Placebo p-value laboratory studies >98% of fleas were killed within 36 hours. Results occurs, then flush eyes copiously with water. In case of ingestion by of clinical field studies using selamectin monthly demonstrated topical dose in 5- to 8-month-old beagles did not cause any adverse A total of 211 dogs were included in the field study safety analysis. Adverse reactions reported in dogs treatewithd N 91 40 RILEXINE Chewable Tablets and placebo are summarized in Table 1. a human, contact a physician immediately. The safety data sheet >90% control of flea infestations within 30 days of the first dose. reactions. In a pre-clinical study selamectin was dosed orally to Success 64 (70.3%) 5 (12.5%) 0.0009 Table 1: Number of Adverse Reactions* Reported During the Field Study withRILEXINE Chewable Tablets (SDS) provides more detailed occupational safety information. To Dogs and cats treated with selamectin, including those with pre- ivermectin-sensitive collies. Oral administration of 2.5, 10, and Failures 27 35 report suspected adverse drug events, for technical assistance or to existing flea allergy dermatitis, showed improvement in clinical signs 15 mg/kg in this dose escalating study did not cause any adverse ADVERSE RILEXINE Placebo *Absence of lesions at the end of the study. obtain a copy of the SDS, contact Virbac AH, Inc. at 1-800-338-3659 associated with fleas as a direct result of eliminating the fleas from reactions; however, eight hours after receiving 5 mg/kg orally, one Tablets or us.virbac.com. avermectin-sensitive collie became ataxic for several hours, but did REACTION n = 145 n = 66 PALATABILITY: The palatability of RILEXINE Chewable Tablets was evaluated in two separate multi-location studies.In the animals and their environment. Number of dogs the first study, 39 client-owned dogs were dosed with RILEXINE Chewable Tablets at 22 mg/kg and evaluated for For additional information about adverse drug experience If the dog or cat is already infested with fleas when the first dose not show any other adverse reactions after receiving subsequent with adverse 50 (34%) 22 (33%) palatability of the product. Palatability testing was performed twice daily prior to feeding for 7 days. Dogs freely reporting for animal drugs, contact FDA at 1-888-FDA-VETS of selamectin is administered, adult fleas on the animal are killed doses of 10 and 15 mg/kg orally. In a topical safety study * reactions consumed (from empty bowl or open hand) 80.8% of their doses. In a second study, 64 client-owned dogs enrolled in or http://www.fda.gov/reportanimalae. and no viable fleas hatch from eggs after the first administration. conducted with avermectin-sensitive collies at 1, 3 and 5 times the # of Each # of Each the field efficacy study were evaluated in a similar manner and freely consumed 78.4% of their doses. recommended dose of selamectin, salivation was observed in all Event* Event* Flammable - Keep away from heat, sparks, open flames or other However, an environmental infestation of fleas may persist for a Vomiting 29 9 ANIMAL SAFETY: RILEXINE Chewable Tablets were administered orally three times a day to 12-week-old healthy sources of ignition. short time after beginning treatment with selamectin because of treatment groups, including the vehicle control. Selamectin also Beagles at 0 mg/kg (placebo), 22 mg/kg (1X), 66 mg/kg (3X), and 110 mg/kg (5X) for 12 weeks, and at 22 mg/kg twice a was administered at 3 times the recommended dose to heartworm Diarrhea 19 6 Do not use in sick, debilitated or underweight animals the emergence of adult fleas from pupae. day for 12 weeks. The most common clinical findings included epiphora, salivation, vomiting and diarrhea among all the infected dogs, and no adverse effects were observed. Anorexia 13 2 dose groups. Three dogs had decreased activity (1 in each from the 22 mg/kg twice a day, 22 mg/kg three times a day, (see SAFETY). Lethargy 9 3 and the 66 mg/kg three times a day groups). These observations were mild and sporadic. Heartworm Prevention in Dogs and Cats CATS: In safety studies, selamectin was applied at 1, 3, 5, and 10 Pruritus 5 0 For the prevention of heartworm disease, SENERGY must be There were increases in alanine aminotransferase (ALT) in the 110 mg/kg three times a day group and in the 22 mg/ PRECAUTIONS: times the recommended dose to six-week-old kittens. No adverse Dermatitis 4 3 kg twice a day group that increased in a dose-dependent pattern. There was an increase in sorbitol dehydrogenase Prior to administration of SENERGY, dogs should be tested for administered on a monthly basis. SENERGY may be administered reactions were observed. The safety of selamectin administered Skin Lesions 5 1 (SDH) in the 110 mg/kg three times a day group compared to the controls. These changes were minimal and the values existing heartworm infections. At the discretion of the veterinarian, year-round or at least within one month after the animal’s first orally also was tested in case of accidental oral ingestion. Oral Otitis Externa 4 2 remained within expected historical control ranges. There were several decreases in total protein (in the 110 mg/kg exposure to mosquitoes and monthly thereafter until the end of Polydipsia 2 2 infected dogs should be treated to remove adult heartworms. administration of the recommended topical dose of selamectin three times a day group) and/or globulin (in the 22, 66, and 110 mg/kg three times a day groups) compared to the the mosquito season. The final dose must be given within one month Somnolence 2 0 controls. These changes resulted in occasional increases in albumin/globulin ratios. Although a drug effect cannot be Selamectin is not effective against adult D. immitis and, while to cats caused salivation and intermittent vomiting. Selamectin Flatulence 1 1 ruled-out, these changes were not clinically relevant. the number of circulating microfilariae may decrease following after the last exposure to mosquitoes. If a dose is missed and a monthly also was applied at 4 times the recommended dose to patent interval between dosing is exceeded then immediate administration Tachypnea 1 1 A mild prolongation in prothrombin time (PT) was observed in the 22 mg/kg three times a day group. This was not treatment, selamectin is not effective for microfilariae clearance. heartworm infected cats, and no adverse reactions were observed. *Some dogs may have experienced more than one adverse reaction or more than one occurrence of the considered clinically relevant due to the small change that remained within the reference ranges. Hypersensitivity reactions have not been observed in dogs with of SENERGY and resumption of monthly dosing will minimize In well-controlled clinical studies, selamectin was used safely in same adverse reaction during the study. the opportunity for the development of adult heartworms. When One dog in the 110 mg/kg three times a day group had moderate amounts of bilirubinuria at the Week 8 and Week 12 patent heartworm infections administered three times the animals receiving other frequently used veterinary products such No clinically significant differences were samplings. No clinical significance was noted. recommended dose of selamectin. Higher doses were not tested. replacing another heartworm preventive product in a heartworm as vaccines, anthelmintics, antiparasitics, antibiotics, steroids, observed in the mean values for all laboratory disease prevention program, the first dose of SENERGY must be collars, shampoos and dips. tests including urinalysis between RILEXINE Chewable Tablets and placebo-treated dogs. At the end of treatment, Cephalexin was not present in any Day 1 samples prior to dosing or in any control animals. After dosing, ADVERSE REACTIONS: cephalexin was well absorbed into systemic circulation of the treated dogs. Within gender and dosage given within a month of the last dose of the former medication. group means for neutrophils, WBC, and globulin values were significantly higher in the placebo group than in Pre-approval clinical trials: STORAGE CONDITIONS: Store below 25°C (77°F). the RILEXINE Chewable Tablets group; whereas, group mean values for eosinophils, A/G Ratio values, and total level, Week 8 mean trough concentrations were generally higher than the Week 4 and 12 mean trough Selamectin, the active ingredient in SENERGY, is a macrocyclic protein values were significantly higher in theRILEXINE Chewable Tablets group than in the placebo group. For all six concentrations (between a 0.9 and 3.6-fold difference). The geometric mean plasma cephalexin trough Following treatment with selamectin, transient localized alopecia lactone compound. These compounds effectively prevent the concentration following three times daily administration of the 110 mg/kg dose was 11.2 µg/mL compared to HOW SUPPLIED: Available in eight separate dose strengths for of these parameters, the differences were not clinically significant and the mean values for each of the parameters with or without inflammation at or near the site of application development of adult heartworms when administered to dogs remained within the normal range. 2.6 µg/mL and 8.7 µg/mL following 22 mg/kg and 66 mg/kg, respectively at Week 12. Geometric mean plasma dogs and cats of different weights (see DOSAGE). SENERGY for cephalexin trough concentrations following administration of 22 mg/kg twice daily were 0.7, 1.3, and 1.0 µg/mL at was observed in approximately 1% of 691 treated cats. Other signs and cats within one month of exposure to infective (L3) Dirofilaria puppies and kittens is available in cartons containing 3 single To report suspected adverse drug events and/or obtain a copy of the Safety Data Sheet (SDS) or for technical Weeks 4, 8, and 12, respectively. observed rarely (≤0.5% of 1743 treated cats and dogs) included immitis larvae. Efficacy of macrocyclic lactones decreases dose tubes. SENERGY for cats and dogs is available in cartons assistance, contact Virbac at 1-800-338-3659. For additional information about adverse drug experience reporting for vomiting, loose stool or diarrhea with or without blood, anorexia, below 100% in dogs, however, if first administered >2 months animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/AnimalVeterinary/SafetyHealth STORAGE INFORMATION: Store at 20°C-25°C (68°F-77°F), with excursions permitted between 15°C-30°C (59°F-86°F). containing 3 single dose tubes. lethargy, salivation, tachypnea, and muscle tremors. after exposure to infective larvae. Thus, in heartworm endemic INFORMATION FOR DOG OWNERS: Owners should be advised that RILEXINE Chewable Tablets are designed totaste HOW SUPPLIED: RILEXINE (cephalexin tablets) Chewable Tablets are supplied in 150 mg, 300 mg, and 600 mg tablets packaged in bottles of 100 tablets. regions, delaying initiation of heartworm prevention using good. Owners should be instructed to keep the product in a secured storage area out of the reach of pets in order to prevent Post-approval experience: SENERGY beyond 2 months of first exposure to infective larvae accidental ingestion or overdose. Post approval experience has shown that dogs and cats may willingly consume more than Approved by FDA under NADA # 141- 326 In addition to the aforementioned clinical signs that were reported the recommended dosage of RILEXINE Chewable Tablets. Adverse reactions may occur if large quantities of tablets are (e.g., starting puppies and kittens at >8 weeks of age), or gaps of ingested (see Precautions, Adverse Reactions, and Animal Safety sections). Distributed by: Virbac AH, Inc. in pre-approval clinical trials, there have been reports of pruritus, >2 months in the administration of SENERGY during periods of Fort Worth, TX 76137 USA urticaria, erythema, ataxia, fever, and rare reports of death. There Owners should be advised to contact their veterinarian immediately and notify Virbac 1-800-338-3659 ( ) if the dog ingests heartworm transmission, increases the risk of the animal acquiring Distributed by: 150 mg 302054 - 05, 300 mg 302055-05 , 600 mg 302056-05 have also been rare reports of seizures in dogs (see WARNINGS). more tablets than prescribed or if other pets ingest RILEXINE Chewable Tablets. In the case of accidental ingestion by heartworms. Animals with unknown heartworm history that test Virbac AH, Inc. Revision date 7/2018 humans, contact a physician immediately. DOSAGE: negative for heartworms prior to the initiation of SENERGY may be P.O. Box 162059 1 harboring pre-patent infections at the time SENERGY was started. CLINICAL PHARMACOLOGY: Cephalexin belongs to the cephalosporin family of bactericidal antibiotics. Birchard SJ and Sherding RG. Saunders Manual of Small Animal Practice, 2nd edition. W.B. Saunders Co. 2000: p. 166. The recommended minimum dose is 2.7 mg selamectin per pound Fort Worth, TX 76161 2 th Testing such animals 3–4 months after initiation of SENERGY Cephalexin is readily and almost completely absorbed following oral administration (90% absolute bioavailability). Blood Adams HR. Veterinary Pharmacology and Therapeutics, 8 edition, 2001, p. 825. (6 mg/kg) of body weight. Approved by FDA under ANADA # 200-670 concentrations are proportional to dose within the range of at least 15 to 45 mg/kg. Binding to canine plasma proteins is low, would be necessary to confirm their negative heartworm status. ranging from 9 to 13% for cephalexin concentrations of 0.5 to 100 µg/mL. RILEXINE is a registered trademark of Virbac S.A. Administer the entire contents of a single dose tube (or two ©2020 Virbac Corporation. At the discretion of the veterinarian, cats ≥6 months of age may be tubes used in combination for dogs weighing over 130 pounds) All Rights Reserved. Food reduces the peak cephalexin concentrations but has negligible effect on the extent of absorption. © 2018 Virbac Corporation. All Rights Reserved. tested to determine the presence of existing heartworm infections of SENERGY topically in accordance with the following tables. (See SENERGY™ before beginning treatment with SENERGY. Cats already infected ADMINISTRATION for the recommended treatment intervals.) with adult heartworms can be given SENERGY monthly to prevent ©2019 Virbac Corporation. All Rights Reserved. RILEXINE is a registered trademark of Virbac Corporation. 5/19 further infections. LA13661

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untreated control group. On Day 42 and Day 84, the presence of wounds INFORMATION FOR DOG OWNERS dosing variability). Control dogs (0 mg/kg) received a vehicle control at was 27.1% (16/59) and 1.8% (1/57), respectively, in the STELFONTA group. a volume equal to the 0.075 mg/kg dose. The intravenous route was • Insert and embed the needle in the tumor through a single injection site and period of three months. See Pictures 1 and 2 below. A separate needle stick injury Owners should be given the Client Information Sheet to read before Exudate from the treated site including serous, serosanguinous, STELFONTA is administered and should be advised to observe their dog chosen for this study because subcutaneous injection was too toxic and draw the syringe plunger back slightly to ensure STELFONTA is not injected into was reported with a maximum potential dose of 0.1 mL tigilanol tiglate into the intratumoral administration was not possible. a blood vessel. While applying even pressure on the syringe plunger, move the distal extremity of the left index finger, resulting in a localized burning sensation, sanguineous, seropurulent, and purulent discharges were seen mainly on for potential side effects, including signs of degranulation and excessive needle back and forth in a fanning manner to inject STELFONTA into the tumor. local inflammation, bruising, muscular pain up the left arm, and localized tissue Day 7 and to a lesser extent on Day 14. Sloughing of the treated site was wound formation, as described in the sheet. Advise dog owners about There were twelve dogs per group (6 male, 6 female). Four dogs/sex/ See Figure 1. The drug should fully perfuse the entire tumor. necrosis. Muscular pain resolved in the first 12-24 hours and the wound healed in observed from Day 7 to Day 42, with decreasing frequency after Day 7. possible adverse reactions, when to contact a veterinarian, and how to group were necropsied two days following the last dose and two dogs/ Peripheral pitting or non-pitting edema and erythema of the surrounding care for the treated tumor site. sex/group were necropsied following a 2-week recovery period. • When the total dose of STELFONTA has been administered, pause to allow 8 weeks. There have been other needle stick injuries reported, with at least one injection into a thumb, with minimal (stinging, pain, and swelling) to no adverse area were observed from Day 7 to Day 28, with decreasing intensity and Some discharge from the site following treatment is expected. The site All dogs survived the study, and there were no STELFONTA-related tissue dispersion before removing the needle from the tumor. Pull back on the frequency after Day 7. Necrotic eschar and epithelialization of the treated syringe plunger to create a small negative pressure before removing the needle events associated with these accidental self-injections. can be cleaned with warm water as necessary. Advise owners to wear effects on body weight, body temperature, ophthalmic exam, site was observed from Day 7 to Day 84, with decreasing frequency after Day disposable gloves when cleaning the area. electrocardiographic parameters, and organ weights. to minimize leakage from the injection site. Picture 1. Thirteen days after Picture 2. Seventy-four days after 14. Granulation or hyper-granulation of the treated site was observed from The following were observed only in dogs in the groups administered For intratumoral injection in dogs only • After the needle is withdrawn, apply light pressure for 30 seconds over the self-injection self-injection Day 7 to Day 84, with decreasing frequency after Day 14. CLINICAL PHARMACOLOGY needle exit hole using a gloved finger. If leakage does occur, rinse injection site STELFONTA: decreased food consumption from Days 22-29, vomiting/ The average wound size at Day 7 for a STELFONTA treated dog was 3.3 cm Antineoplastic with saline to wash STELFONTA from the skin surface. Do not re-administer. Mechanism of Action retching during infusion or immediately post-infusion, wound x 2.4 cm (original average tumor size 1.9 x 1.6 x 0.9 cm). On Day 28, the In non-clinical pharmacology studies, tigilanol tiglate has been shown to formation at the infusion site after the second or third dose, decrease Single use vial • To minimize risk of accidental self-injection, do not recap the needle. Dispose of average wound size was 2.0 x 1.4 cm. the needle and syringe. have three inter-related effects that are responsible for its anti-tumor in activity sporadically throughout the study, and elevations in alanine The largest total wound for a STELFONTA treated dog was reported seven effectiveness. The first effect is to cause oncolysis of tumor cells that are aminotransferase on Day 23.

WARNING: SEVERE WOUND FORMATION IN HUMANS; days after treatment. The treated tumor was located on the left caudal stifle in direct contact with tigilanol tiglate. The oncolysis occurs within the first The following were observed in all groups, including vehicle control EXTENSIVE WOUND FORMATION, MAST CELL DEGRANULATION, and the original tumor size measured 2.4 x 2.1 x 1.4 cm. The wound area hours following treatment and results from the disruption of mitochondrial and increased in a dose dependent manner: limited use of the leg that AND DEATH IN DOGS DUE TO MAST CELL DEGRANULATION initially consisted of three individual wounds recorded on the treated limb functioning. Secondly, at the same time, tigilanol tiglate activates a protein received the infusion occurred soon after dosing, weakness after the Human Safety Field Study (both medial and lateral sides): 7.5 x 4.5 cm, 7.0 x 3.5 cm, and 11.5 x 7.0 cm. kinase C (PKC) signaling cascade which propagates throughout the tumor, first dose, salivation and infusion site edema and erythema increased The wounds had reduced to 3.5 x 1.4 cm, 3.9 x 1.5 cm, and 9.7 x 4.3 cm resulting in an acute inflammatory response with swelling and erythema • Accidental self-injection of STELFONTA® may cause severe In a well-controlled, multi-center, randomized, double-masked field study in frequency and severity throughout the study, and tremors occurred 28 days after treatment, and 0.5 x 0.7 cm and 2.5 x 2.9 cm 42 days after extending to the tumor margins and immediate surroundings. This immediately post-infusion and increased in severity with dose. wound formation. To decrease the risk of accidental self- evaluating the effectiveness and safety of STELFONTA for the treatment of treatment and were no longer present at 84 days after treatment. inflammatory response is normal and necessarily contributes to the activity injection, sedation of the dog may be necessary (see Dosage cutaneous and subcutaneous mast cell tumors in dogs, 117 dogs treated with of tigilanol tiglate by (a) restricting blood and oxygen supply to the tumor Vomiting, retching, or tremors were typically transient and resolved within and Administration, Human Warnings and Adverse Reactions). STELFONTA and 42 dogs receiving sham treatment (untreated control) were One dog treated with STELFONTA was reported with an extensive wound 1 hour of dosing while salivation also typically resolved within 4 hours. formation (wound size 25.0 x 9.5 cm) with severe tissue slough (Grade (causing localized hypoxia) and (b) recruiting and activating innate immune Dog Safety evaluated for safety. Eighty-one dogs were treated with STELFONTA on Day 0. cells (principally neutrophils and macrophages), which then target the tumor Loose feces were observed in all groups in a non-dose dependent manner. Thirty-six previously untreated control dogs were treated with STELFONTA on 3) nine days after treatment of a mast cell tumor on the left metacarpal area (original tumor size 2.5 x 1.9 x 1.3 cm). The wound extended and release reactive oxygen species, proteases, and cytokines that function Polydipsia occurred in the control, 0.05 and 0.075 mg/kg groups. Trending • Always administer a corticosteroid (e.g. prednisone Day 30. In addition, 18 dogs treated with STELFONTA on Day 0 had the same towards decreasing hematocrit (but still within reference intervals) was or prednisolone), an H1 receptor blocking agent (e.g. proximally up the leg to the shoulder and required bandaging of the leg in an antimicrobial role. This acute inflammatory response generally resolves Figure 1: Dispersion of STELFONTA throughout the tumor. tumor re-treated with STELFONTA on Day 30 due to incomplete response. The within 48 to 96 hours. The third component of the antitumor activity of observed in all groups. One dog in the 0.05 mg/kg group was mildly anemic diphenhydramine), and an H2 receptor blocking agent (e.g. most common adverse reactions included wound formation, injection site and antibiotics. Scar contracture formed, requiring treatment under sedation to release the scar tissue. Clinical pathology abnormalities tigilanol tiglate is associated with direct effects of the drug in increased during recovery. Monocytosis and elevated fibrinogen were seen on Days famotidine) when treating with STELFONTA to decrease the CONTRAINDICATIONS pain, lameness in the treated limb, vomiting, diarrhea, and hypoalbuminemia. 2 and 23 in a dose-dependent manner. potential for severe systemic adverse reactions, including Wound formation, vomiting, and diarrhea were mainly observed within the first included elevated band neutrophils, anemia, and hypoalbuminemia. permeability of the tumor vasculature (via activation of the Beta-II isoform death, from mast cell degranulation (see Contraindications and Do not inject STELFONTA into subcutaneous mast cell tumors located above the The wound had not fully healed by the end of the study 89 days after of PKC) leading to tumor vascular destruction. The resulting outcome is Gross pathology findings at the infusion site included inflammation, elbow or hock (e.g. on the body, head, or neck). This may result in accumulation of 7 to 10 days after treatment. Injection site pain and lameness in the treated leg Dosage and Administration). were mainly observed within the first 2 days after treatment. Hypoalbuminemia treatment. See pictures below comparing progression of this extensive tumor destruction with a deficit or wound remaining where the tumor redness, and thickening of the skin. Correlative histopathology findings • Do not inject STELFONTA into subcutaneous mast cell tumors necrotic debris in the subcutaneous space increasing the risk of systemic adverse wound formation versus commonly observed wound progression. was located. Complete healing of the resulting wound following tumor of the infusion site included hemorrhage, edema, inflammation, mixed reactions, including death, from mast cell degranulation (seeAdverse Reactions). was mainly observed within the first 28 days after treatment. All dogs received located above the elbow or hock (e.g. on the body, head, or concomitant medications as noted in the Effectiveness section. The adverse destruction by STELFONTA is typically within 6 weeks. cell infiltration, fibrosis, and chronic organizing thrombosis. Only one neck). This may result in accumulation of necrotic debris in the WARNINGS reactions during the study are summarized in Table 2 below. Pharmacokinetics of the recovery dogs had changes at the infusion site consisting of subcutaneous space increasing the risk of systemic adverse Typical wound Extensive wound proliferation of the intima. One dog in the 0.075 mg/kg group had a Human Safety Table 2: Adverse Reactions During the Field Study Pharmacokinetic properties of STELFONTA were evaluated in a pilot study reactions, including death, from mast cell degranulation (see monitoring systemic levels following intratumoral injection, with a dose severe wound, confirmed on histopathology as ulcerative inflammation Contraindications, Warnings and Adverse Events). NOT FOR USE IN HUMANS. KEEP THIS AND ALL MEDICATIONS OUT OF REACH 3 and severe necrosis with bacteria present. Gross pathology findings also OF CHILDREN. STELFONTA STELFONTA UNTREATED delivered according to the size of the mast cell tumor. A dose of 0.5 mg/cm • Treatment with STELFONTA has been associated with cellulitis Adverse Reaction 1st Treatment 2nd Treatment CONTROL (0.5 mL/cm3) was used in dogs with tumor volumes ranging from 0.1 to 6.8 included red, mottled, firm, and enlarged lymph nodes in all dose groups, and severe tissue sloughing extending away from the treated Caution is required during treatment to avoid accidental self-injection. Dogs (n = 117) (n = 18) (n = 42) cm3 resulting in doses ranging from 0.002 mg/kg to 0.145 mg/kg and total including recovery dogs, confirmed on histopathology as inflammation, site resulting in extensive wounds that require additional undergoing treatment with STELFONTA should be adequately restrained and Seven Days doses ranging from 0.05 mg to 3.4 mg per dog. A total of 6 cutaneous and 5 lymphoid hypercellularity, hemorrhage, and sinus histiocytosis. Pituitary treatment and prolonged recovery times (see Warnings, sedation used if necessary. Use a Luer-lock syringe to administer STELFONTA. Do Wound formation 110 (94.0%) 12 (66.7%) 3 (7.1%) after treatment subcutaneous mast cell tumors were treated in 10 dogs (one dog had two cysts were observed in 7 dogs in all STELFONTA treated groups. One Precautions and Adverse Events). not recap the needle. Accidental self-injection may result in local inflammatory dog each from the 0.075 mg/kg group was observed to have kidney Injection site pain 61 (52.1%) 7 (38.9%) 1 (2.4%) tumors treated consecutively). The following range of pharmacokinetic reactions, including swelling, redness and severe wound formation. In case of parameters were determined for STELFONTA in plasma: 1) elimination half- tubular vacuolation, dilation of the ventricles of the brain, and chronic accidental self-injection, immediately rinse the area with water, seek medical advice Lameness in treated life (t ): 2.85 to 36.87 hours; 2) maximum plasma concentration (C ): 0.356 inflammation of both the left thigh skeletal muscle and left sciatic nerve. 29 (24.8%) 2 (11.1%) 1 (2.4%) ½ max CAUTION immediately, and show the package insert to the physician. limb ng/mL to 13.8 ng/mL; and 3) area under the plasma concentration time- Laboratory Cardiovascular Study Federal law restricts this drug to use by or on the order of a licensed veterinarian. Wear personal protective equipment consisting of disposable gloves, protective eye curve to the last quantifiable plasma concentration (AUC ): 2.25 h*ng/mL Vomiting 24 (20.5%) 3 (16.7%) 4 (9.5%) last In a 12-day laboratory cardiovascular study, 4 healthy male conscious wear, and a lab coat or gown when handling STELFONTA. STELFONTA is an irritant and to 31.24 h*ng/mL. There was no relationship between drug exposure (C telemeterized Beagle dogs approximately 2-4 years old were administered DESCRIPTION accidental exposure to skin, eye, or by ingestion should be avoided. In case of dermal max Diarrhea 24 (20.5%) 3 (16.7%) 2 (4.8%) and AUClast) with tumor location (cutaneous or subcutaneous) or with total STELFONTA as a single intravenous infusion. Treatment consisted of four The active ingredient for tigilanol tiglate injection is a phorbol ester that activates or ocular exposure, repeatedly wash the exposed skin or eye with water. If wearing Fourteen Days dose. In an evaluation of the pharmacokinetic data from the 5 dogs with groups: vehicle control and STELFONTA at doses of 0.01, 0.025 and 0.075 alpha, beta I, beta II, and gamma isoforms of protein kinase C. The chemical name is contacts, rinse the eyes first then remove contacts and continue to rinse with water. Hypoalbuminemiaa 21 (18.0%) 2 (11.1%) 1 (2.4%) after treatment cutaneous tumors, dose levels ranged from 0.002 mg/kg to 0.145 mg/kg. mg/kg body weight. All four dogs received all treatments with at least a (4S,5S,6R,7S,8R,9R,10S,11R,12R,13S,14R)-12-(2E)-2-methylbut-2-enoatyl-13-[(2S)-2- If symptoms such as local signs of redness and swelling occur, or if there has been The highest Cmax was 11.1 ng/mL and the highest AUClast was 31.24 h*ng/mL 3-day wash-out period. methylbutyroyl]-6,7-epoxy-4,5,9,12,13,20-hexahydroxy-1-tigliaen-3-one. The molecular ingestion, seek the advice of a physician and show them the package insert. Injection site bruising/ at a dose of 0.125 mg/kg. For the other 5 dogs with subcutaneous tumors, formula is C30H42O10 and its molecular weight is 562.65 g mol-1. Each mL of STELFONTA erythema/edema/ 20 (17.1%) 3 (16.7%) 1 (2.4%) All dogs survived the study and there were no STELFONTA-related Limited data is available on the potential teratogenic effects of STELFONTA. doses ranged from 0.049 mg/kg to 0.094 mg/kg. The highest Cmax was 13.8 effects on body temperatures, blood pressure, or electrocardiograms. contains 1 mg tigilanol tiglate and sterile water for injection (60% v/v), propylene glycol Therefore, STELFONTA should not be administered by women who are pregnant irritation ng/mL and the highest AUC was 30.81 h*ng/mL at a dose of 0.094 mg/kg. (40% v/v), sodium acetate (<0.1% w/v), and glacial acetic acid (<0.1% w/v). last The following were observed only after administration of STELFONTA or planning to become pregnant. Anorexia 14 (12.0%) 2 (11.1%) 3 (7.1%) The chemical structure for tigilanol tiglate is: EFFECTIVENESS in all dose groups: salivation, vocalization, incoordination, tremors, red People with known hypersensitivity to tigilanol tiglate or to any of the excipients Regional lymph node feces, and decreased feces output. Retching, vomiting, incoordination, should avoid contact with STELFONTA. 13 (11.1%) 1 (5.6%) 1 (2.4%) The effectiveness of STELFONTA was evaluated in a well-controlled, and changes in activity levels (increased and decreased) occurred in the swelling/enlargement Twenty-Eight Days multi-center, randomized, double-masked, field study in client-owned Animal Safety 0.075 mg/kg group only. Tachycardia was seen for the first 2.5 hours Tachycardia 12 (10.3%) 0 (0.0%) 1 (2.4%) after treatment dogs. Enrolled dogs had non-metastatic World Health Organization after the 0.075 mg/kg dose only. The following were observed after Dogs should be monitored during and for 5-7 days after intratumoral treatment stages Ia (one tumor confined to the dermis, without regional lymph node administration of control or STELFONTA: excessive panting, decreased with STELFONTA for signs of systemic mast cell degranulation such as vomiting, Weight loss 12 (10.3%) 3 (16.7%) 5 (11.9%) involvement) and IIIa (multiple dermal tumors; large infiltrating tumors appetite, and limited usage/swelling of leg or paw. All dogs lost weight diarrhea, lethargy, anorexia/hyporexia, altered breathing, hypotension, urticaria, without regional lymph node involvement) mast cell tumors that were (i) during the study. Clinical signs resolved around 4 hours post dosing. edema at or away from the treated site, or bruising at or away from the treated Cystitis 10 (8.6%) 1 (5.6%) 2 (4.8%) cutaneous, or (ii) subcutaneous and located at or distal to the elbow or the Pilot Field Study site. If signs are observed, appropriate treatment should be started immediately. Dermatitis 9 (7.7%) 1 (5.6%) 1 (2.4%) hock). A total of 123 client-owned dogs with a mast cell tumor measuring Always administer the recommended concomitant medications (corticosteroids, less than or equal to 10 cm3 were randomized to treatment with a single In a 28-day unmasked field study, 10 client-owned dogs, 6-14 years old H1, and H2 receptor blocking agents) with STELFONTA. Death has occurred Personality/behavior injection of STELFONTA (n=81) or untreated control (n=42). On the day of were administered tigilanol tiglate (non-commercial formulation) once 8 (6.8%) 0 (0.0%) 2 (4.8%) 3 3 following mast cell degranulation when these concomitant medications were not change Eighty-Four Days treatment, the average tumor volume was 1.7 cm (range 0.1 to 9.8 cm ). as an intratumoral injection at a dose of 0.5 mg tigilanol tiglate per cubic centimeter (cm3) of tumor volume, not exceeding 0.25 mg/kg body weight administered according to this Package Insert (see Dosage and Administration Infection at injection 8 (6.8%) 0 (0.0%) 0 (0.0%) after treatment A total of 118 dogs were included in the effectiveness analysis; 80 dogs were and Adverse Reactions). site in the STELFONTA group and 38 dogs were in the untreated control group. (maximum dose of 5 mg). One dog was enrolled a second time to treat a 2 second mast cell tumor after successful treatment of the first tumor. See INDICATION STELFONTA can induce a substantial local inflammatory reaction which may result Tachypnea 7 (6.0%) 2 (11.1%) 1 (2.4%) Response to treatment was evaluated using the RECIST , where complete STELFONTA injection is indicated for use in dogs for the treatment of: in pain, bruising, and swelling. During this time, an analgesic may be needed in response (CR) is resolution of the target tumor, partial response (PR) is at pharmacokinetic results from this study under Clinical Pharmacology. • non-metastatic cutaneous mast cell tumors addition to the use of corticosteroids and both H1 and H2 receptor blocking agents. Pruritus 6 (5.1%) 3 (16.7%) 2 (4.8%) least a 30% decrease in the longest diameter of target tumor, stable disease The most common observations after tigilanol tiglate administration (SD) is a decrease of less than 30% or increase of less than 20% of the longest were injection site reactions including necrosis, swelling (localized • non-metastatic subcutaneous mast cell tumors located at or distal to the elbow Treatment with STELFONTA causes tumor necrosis which is part of the mechanism Lethargy/Depression 6 (5.1%) 1 (5.6%) 1 (2.4%) One dog treated with STELFONTA was reported with a bacterial infection of action of the drug. Bruising, heat, pain, and swelling may begin at the site diameter of the target tumor, and progressive disease (PD) is greater than a edema and edema extending well beyond the tumor injection site), pain, or the hock and cellulitis in the right rear leg 9 days after treatment of a mast cell 20% increase in the longest diameter of the target tumor. restlessness, inflammation, erythema, bleeding ulcerations, bruising/ within 2 hours of treatment. By day 7 after treatment, wound formation including Pyrexia 3 (2.6%) 2 (11.1%) 0 (0.0%) tumor on the right rear paw. There was bruising of the upper thigh and full thickness dermal necrosis with exudate, peripheral tissue edema, erythema, The primary effectiveness variable compared CR rates of the target discoloration, sloughing of tissue, open wound, mild drainage, malodor, DOSAGE AND ADMINISTRATION a necrotic skin on the caudal right thigh and cranial aspect of the hock. skin discoloration, tissue sloughing, and necrotic eschar may occur. There was a statistically significant decrease in albumin and albumin/globulin tumor between groups 28 days after treatment. At 28 days after and presence of granulation tissue. Three dogs experienced dermatitis ALWAYS PROVIDE THE CLIENT INFORMATION SHEET TO THE DOG OWNER ratios at Day 7 in the STELFONTA group compared to the control group. The Bloody discharge under the necrotic tissue revealed rod bacteria and toxic treatment, a statistically significantly greater proportion of dogs in the with or without skin necrosis in a region nearby but distinct from the BEFORE DOSE ADMINISTRATION. In addition to tumor necrosis, treatment with STELFONTA has been associated hypoalbuminemia ranged from 2.0 to 2.6 g/dL (reference range 2.7-3.9 g/dL). neutrophils. The dog was treated with intravenous fluids and antibiotics. tumor injection site. One dog experienced non-weight bearing lameness, with cellulitis and severe tissue sloughing extending away from the treated site STELFONTA treated group (60/80; 75%) achieved CR compared to dogs Concomitant medications Note: If an animal experienced the same adverse reaction more than once, only Systemic Mast Cell Degranulation and Death in the untreated control group (2/38; 5.3%) (p<0.0001). An objective muscle atrophy and enlarged popliteal lymph node. One dog vomited resulting in extensive wounds (see Adverse Reactions). after administration. Three dogs required longer healing times beyond Administer the following medications to decrease the potential for severe the highest grade was tabulated. Two dogs from two separate pilot studies died from a suspected mast tumor response (CR + PR) was observed in 64/80 (80%) of the STELFONTA systemic adverse reactions from mast cell degranulation: Do not inject STELFONTA into normal subcutaneous tissue or adjacent tissues treated dogs. Of the 60 dogs in the STELFONTA group that experienced 28 days, with the longest requiring 5 months. Hypoalbuminemia was (e.g. beyond tumor margins) because severe edema, erythema and necrosis of Adverse reactions were graded using the Veterinary Co-operative Oncology cell degranulation reaction. Both dogs were treated with STELFONTA observed in 5 dogs with hypoproteinemia observed in 1 of these 5 dogs 1 CR at Day 28, response assessment was conducted for 59 dogs at Day 42 • Corticosteroid (e.g. oral prednisone or prednisolone at anti-inflammatory the injected tissue may occur. Group – Common Terminology Criteria for Adverse Events (VCOG-CTCAE). for a subcutaneous mast cell tumor located above the hock and did not on Day 7 and was resolved by Day 28. dose): Start medication 2 days prior to STELFONTA treatment and continue for Most adverse reactions were Grade 1 (mild) or 2 (moderate). Grade 3 (severe) receive the concomitant medications as prescribed. and for 57 dogs at Day 84. At Day 42, 59/59 (100%) were disease-free at 8 days post-treatment (10 days total). PRECAUTIONS and 4 (life-threatening) adverse reactions in dogs treated with STELFONTA the injection site, and at Day 84, 55/57 (96%) were disease-free at the STORAGE INFORMATION In a pilot field study, one dog with a large (10 cm³) subcutaneous mast injection site. • H1 receptor blocking agent (e.g. oral diphenhydramine): Start medication on STELFONTA has not been evaluated in dogs with signs of systemic disease due to included: lameness in the treated limb (6 dogs), injection site pain (4 dogs), wound cell tumor on the right hip was treated with STELFONTA. The dog Store STELFONTA vials refrigerated at 2°C to 8°C (35°F to 46°F). the day of STELFONTA treatment and continue for a total of 8 days. the mast cell tumor(s). formation (3 dogs), lethargy/depression (3 dogs), anorexia (2 dogs), infection at For all dogs, corticosteroids (prednisone or prednisolone) were initiated injection site (1 dog), pruritis (1 dog), and tachycardia (1 dog). had a partial Response Evaluation Criteria in Solid Tumors Guideline Do not freeze. STELFONTA is not intended for the treatment of metastatic mast cell tumors. (RECIST)2 response to the initial STELFONTA injection and was re-treated 2 days prior to treatment at a dose of 0.5 mg/kg orally twice daily and • H2 receptor blocking agent (e.g. oral famotidine): Start medication on the day continued for 7 days total (2 days before, on the day of treatment and 4 Keep the vial in the carton at all times to protect the vial from light. of STELFONTA treatment and continue for a total of 8 days. The safe and effective use of STELFONTA has not been evaluated for simultaneous Adverse reactions associated with use of the required concomitant with STELFONTA, 30 days following the initial injection. The patient corticosteroids were similarly reported in STELFONTA and untreated control dogs days after treatment), then 0.5 mg/kg once daily for an additional 3 days. For single use only. Dosing Instructions treatment of more than one mast cell tumor. did not receive any of the recommended concomitant medications and included elevated alkaline phosphatase, polyuria, and polydipsia. of prednisolone, chlorpheniramine and famotidine from 24 hours An H1 receptor blocking agent (diphenhydramine [2 mg/kg orally twice Dispose of any unused product in accordance with disposal for routine 3 The safe and effective use of STELFONTA has not been evaluated in dogs with a Administer STELFONTA as an intratumoral injection at a dose of 0.5 mL per cm of after the second STELFONTA injection. On Day 2 following the second daily]) and H2 receptor blocking agent (famotidine [0.5 mg/kg orally twice medical waste. tumor volume, as determined by the following calculations: mast cell tumor volume >10 cm3. Wound Formation daily]) were initiated on the day of treatment and continued for 7 days. STELFONTA injection, the dog became anorexic, painful, and lethargic HOW SUPPLIED • Determine the Tumor Volume in cm3: Use STELFONTA with caution in tumors located within mucocutaneous regions Tumor observations were conducted at 2, 4, 8, and 24 hours and 4 days after and had marked swelling of the right hind limb extending to the chest Other medications prescribed based on veterinary discretion included 0.5 x [length (cm) x width (cm) x height (cm)] (e.g., eyelids, vulva, prepuce, and anus) as tumor necrosis could cause a change in treatment. The 81 dogs treated with STELFONTA on Day 0 were reported with hemorrhagic, ruptured blisters near the hock joint. Blood work antibiotics, analgesics, and sedatives. The majority of antibiotics were STELFONTA is supplied as a sterile, colorless liquid in a 5 mL clear, single- most frequently with swelling, bruising, pain and heat at all tumor observation 3 morphology of the mucocutaneous region resulting in loss of functional integrity. showed anemia, hypoproteinemia, liver enzyme elevations, and used to treat injection site infections. The majority of analgesics were use glass vial containing 2 mL of STELFONTA at a concentration of 1 mg/ • Confirm the Tumor Volume does not exceed 10 cm . Do not use STELFONTA if timepoints. The following were reported at 24 hours post treatment: mL tigilanol tiglate in sterile water for injection. tumor volume is >10 cm3. Use STELFONTA with caution in mast cell tumors with significant ulceration as white blood cell changes (leukocytosis, neutrophilia, monocytosis, used to treat tumor pain and were mainly initiated on the day of or day • Swelling: 97.5% (79/81 dogs) after treatment. Sedatives were used for treatment administration, • Calculate the Dose Volume (mL) of STELFONTA to inject: leakage of the drug from the ulcerated area may occur following treatment and thrombocytopenia). The dog was hospitalized, received a blood REFERENCES potentially reducing effectiveness. conducting diagnostics, anxiety, and temperament issues. Tumor Volume x 0.5 mL • Bruising: 91.4% (74/81 dogs) transfusion, and was administered intravenous fluids, prednisolone, 1. Veterinary Cooperative Oncology Group – common terminology chlorpheniramine and tramadol. Pitting edema progressed to the neck Quality of Life (QoL)3 was assessed by owners throughout the study • Confirm the dose of STELFONTA does not exceed 0.25 mL/kg body weight. The safe use of STELFONTA has not been evaluated in dogs with concurrent • Pain: 69.1% (56/81 dogs) criteria for adverse events (VCOG-CTCAE) following chemotherapy or diseases that may result in delayed wound healing. by four days following treatment. Despite supportive care, the dog died and the mean scores for the QoL assessment was similar between the biologic antineoplastic therapy in dogs and cats v1.1. . • Do not exceed 5 mL per dog, regardless of tumor volume or body weight. • Heat: 53.1% (43/81 dogs) Vet Compar Oncol After treatment with STELFONTA, dogs may require additional care of the treated site five days following treatment likely due to degranulation of the mast cell STELFONTA and untreated control groups at all time points. 20 Jul 2011. At 24 hours post treatment, intact skin was reported in 71.6% (58/81 dogs) of tumor and internal necrotic discharge of the tumor. • The minimum dose of STELFONTA is 0.1 mL, regardless of tumor volume or body to aid in the healing process. An Elizabethan collar or a non-constricting dry gauze ® Eighteen of the 20 STELFONTA treated dogs without CR received a 2. Eisenhauer EA, Therase P, Bogaerts J, Schwartz LH, Sargent D, Ford R, STELFONTA (tigilanol tiglate injection) treated dogs. On Day 4 intact skin was 3 weight. If the calculated dose is <0.1 mL, administer 0.1 mL. bandage may be needed to prevent the dog from self-traumatizing the treated site. In a separate pilot field study, one dog with a moderate (2.53 cm ) second treatment. Twenty-eight days following the second treatment, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd reported in 17.3% (14/81 dogs) of STELFONTA treated dogs. On Day 4, the subcutaneous mast cell tumor on the left caudal hindlimb was treated Administration of STELFONTA: After treatment with STELFONTA, separation from other household animals may following observations were reported with the highest frequency: CR was observed in 8/18 (44.4%) of these dogs. Forty-two days following L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in with STELFONTA. The dog was treated with chlorpheniramine and the second treatment, CR was observed in 7/18 (38.9%) of treated dogs. solid tumors: revised RECIST guideline (version 1.1), Eur J Cancer. 2009; Sedation may be necessary to safely and accurately administer STELFONTA to be necessary to prevent grooming and trauma to the treated site. • Necrosis: 55.6% (45/81 dogs) decrease the chance of accidental self-injection. Wear gloves, eye protection, meloxicam on treatment day (Day 0) and Day 1 only. The dog did not 45(2):228-247. The safe use of STELFONTA under conditions of use has not been evaluated in • Crater pockets: 37.0% (30/81 dogs) receive further concomitant medication. On Day 3 the dog was lethargic TARGET ANIMAL SAFETY and lab coat or gown in the preparation and administration of STELFONTA. Care dogs younger than 3.5 years old. 3. Lynch S, Savary-Bataille K, Leeuw B, Argyle DJ. Development of a should be taken to restrict injections to the tumor only. STELFONTA should not be • Exudate: 37.0% (30/81 dogs) and there was significant edema at the injection site. While intravenous The margin of safety and toxicity of STELFONTA was evaluated in one questionnaire assessing health-related quality-of-life in dogs and cats injected into the margins, beyond the periphery, or deep to the tumor. The safe use of STELFONTA has not been evaluated in dogs that are pregnant, fluid and antibiotic therapy was initiated on Day 3, the dog rapidly laboratory safety study and one laboratory cardiovascular study utilizing with cancer. Vet Compar Oncol. 2011; 9 (3):172-82. lactating, or intended for breeding. • Eschar: 28.4% (23/81 dogs) deteriorated and died on the following day likely due to degranulation final market formulation, and one pilot field study that used non- Approved by FDA under NADA # 141-541 • Shave the tumor site. Avoid manipulation of the tumor. • Ulceration: 11.1% (9/81 dogs) ADVERSE REACTIONS of the mast cell tumor. Pathology findings included widespread cellulitis, commercial formulation. • Draw the calculated volume of STELFONTA into a sterile Luer-lock syringe with panniculitis (likely of bacterial origin), and septic peritonitis. STELFONTA® is a registered trademark of QBiotics Group Limited, used A wound healing assessment was performed on the effectiveness dataset which Laboratory Safety Study a 23 gauge needle. Human Exposure included 80 dogs in the STELFONTA group and 38 dogs in the untreated control under license. To report suspected adverse reactions, to obtain a Safety Data Sheet Distributed by Virbac AH, Inc. • Identify an appropriate injection point on the edge of the tumor. See Figure 1. There was one human exposure during the field study where the veterinarian had a group. Wounds developed in 92.5% (74/80) of STELFONTA treated dogs and (SDS), or for technical assistance, call 800-338-3659. For additional In a 4-week laboratory safety study, 48 healthy Beagle dogs 6 to Insertion of the needle depends on the tumor’s location, form, and appearance. needle stick injury to the thumb at completion of tumor treatment and was injected 2.6% (1/38) of untreated control dogs by Day 7. On Day 28, the presence of 8 months old were administered STELFONTA intravenously over a P.O Box 162059, Version date: August 2020 information about adverse drug experience reporting for animal drugs, Fort Worth, Texas 76161. If a tumor protrudes above the surface of the skin, insert the needle at an with an unknown amount of STELFONTA. The incident resulted in pain and necrosis wounds was 40% (32/80) in the STELFONTA group and 2.6% (1/38) in the contact the FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae. 15-minute infusion once a week for four weeks on Days 1, 8, 15, and 22, PC5111A oblique angle of approximately 45°. of the center of the thumb at the point of needle stick. The wound healed over a at doses of 0, 0.025, 0.05, or 0.075 mg/kg body weight (ranges between Tel. 1-800-338-3659 A-IN-001.01 0.02-0.036, 0.039-0.056, and 0.06-0.08 mg/kg, respectively due to

36 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 37 PRODUCT INSERTS/DISCLOSURES PRODUCT INSERTS/DISCLOSURES

Repeat treatment every 12 months to maintain e–cacy. Appropriate endocrine testing and clinical monitoring should be performed at appropriate intervals to monitor the response to therapy.

CONTRAINDICATIONS

LEGAL STATUS - In order to be legally marketed, a new animal Do not use this product in ferrets with known hypersensitivity to drug intended for a minor species must be Approved, Conditionally deslorelin acetate or other synthetic hormones. Approved, or Indexed by the Food and Drug Administration. THIS PRODUCT IS INDEXED - MIF # 900-013. Extra-label use is HUMAN SAFETY WARNINGS prohibited. FOR USE IN FERRETS ONLY This product is not to be used in animals intended for use as KEEP OUT OF REACH OF CHILDREN. DO NOT HANDLE THIS food for humans or food-producing animals. PRODUCT IF YOU ARE PREGNANT OR NURSING OR SUSPECT YOU MAY BE PREGNANT. Accidental administration may lead to a CAUTION: Federal (USA) law restricts this drug to use by or on the disruption of the menstrual cycle. Avoid direct skin contact with the order of a licensed veterinarian. implant; if skin contact occurs, wash the ažected area immediately with soap and water. The use of gloves is advised. As with all injectable drugs causing profound physiological ežects, routine ® precautions should be employed by practitioners when handling and Suprelorin F using Suprelorin® F (4.7 mg) Implant to prevent accidental injection. In case of accidental human injection, a physician should be (DESLORELIN ACETATE) 4.7 mg Implant consulted and the implant should be removed. PRECAUTION

DESCRIPTION Do not use in animals intended for breeding. The safe use of this product has not been evaluated in pregnant or lactating ferrets. Suprelorin® F (4.7 mg) Implant is a synthetic GnRH analogue (deslorelin acetate) in a biocompatible, slow release subcutaneous ADVERSE REACTIONS implant. The implant is a solid, opaque, white to pale yellow cylinder, 2.3 mm x 12.5 mm in length and weighing 50 mg. The Suprelorin® F It is possible that treated ferrets will exhibit signs of soreness and (4.7 mg) Implant comes pre-loaded in an implanting needle. Each swelling at the implantation site which should resolve over one or implant contains 4.7 mg deslorelin (as deslorelin acetate) in an inert two weeks. Undesirable histology at the site of implantation has not matrix. been reported in other species (canine). Other reported side ežects include: weight gain, lethargy and failure to respond to therapy. Chemical Structure – Deslorelin acetate To report suspected adverse drug events, please call Virbac at 800-338-3659. For additional information about adverse drug experience reporting for animal drugs, contact the FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae.

PHARMACOLOGY

Suprelorin® F (4.7 mg) Implant is a controlled release implant containing the GnRH agonist deslorelin. Deslorelin acetate suppresses the reproductive endocrine system, preventing production of pituitary and gonadal hormones. Deslorelin acetate has not been shown to [(6-D-tryptophan-9-(N-ethyl-L-prolinamide)-10-deglycinamide]GnRH reduce the size of adrenal tumors and is not considered curative.

INDICATIONS DISPOSAL

Suprelorin® F (4.7 mg) Implant is indicated for the management of Each implanting needle (sterile) is a single use device. Used needles adrenal gland cortical disease in the male and female domestic ferret. should immediately be placed in a designated and appropriately labeled "sharps" container. Each actuator syringe (non-sterile) is a DOSAGE AND ADMINISTRATION multi-use device and should be saved for future use with the remaining implant(s) in the carton. Unused implants should be The recommended dosage is one, 4.7 mg implant per ferret every disposed of in accordance with local environmental requirements. 12 months. Appropriate clinical monitoring is suggested to determine that the symptoms of adrenal disease are being STORAGE adequately controlled. Store at temperatures between 2˚ and 8˚ C (36˚ and 46˚ F). Do not use if the foil pouch is damaged. Do not freeze.

Remove Luer Lock cap from the implanting needle. Attach the HOW SUPPLIED actuator syringe to the implanter using the luer lock connection. One implant should be implanting needle subcutaneously at the dorsal Five (5) or two (2) implants pre-loaded in implanting needles and aspect of the base of the neck. Administer only one implant per ferret. individually packaged per carton. Select the implant site by locating the area of the back midway between the shoulder blades. It is not necessary to prepare the For technical assistance, to request an SDS, or to report suspected implantation site. If the hair is long, a small section may be clipped if adverse drug events, please call Virbac at 1-800-338-3659. required. Li’ the loose skin between the shoulder blades. Insert the entire length of the needle subcutaneously. Fully depress the actuator syringe plunger. Press the skin at the insertion site as the needle is Manufactured for: slowly withdrawn, and maintain pressure for 30 seconds. Examine the Virbac AH, Inc. implanting needle to verify that the implant has not remained within P.O. Box 162059 the needle, and that the blue plastic spacer is visible at the tip of the Fort Worth, TX 76161 needle. It may be possible to palpate the implant in situ. The biocompatible implant does not require removal. Wash hands a’er use. Product of Australia MIF 900-013 Revision 11/2020 L-2000-F-US-3

38 VIRBAC PRODUCT GUIDE For more information, call 1-800-338-3659 or visit us.virbac.com For more information, call 1-800-338-3659 or us.virbac.com VIRBAC PRODUCT GUIDE 39

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January 2021 ©2021 Virbac Corporation. All Rights Reserved. BIOVAFLEX® eggshell membrane is an innovative, novel ingredient. BIOVAFLEX® is a registered trademark of Biova, LLC, used under license. ZANTHIN is a registered trademark of U.S. Nutraceuticals LLC, Shaping the future used under license. All trademarks are property of their respective owners. All other of animal health trademarks are property of the Virbac Group of Companies. VRB820-02 11156